The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Fowler, Jack F.

2002-01-01

Background and Purpose: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor

Human normal tissue reactions in radiotherapy

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Taniike, Keiko

1990-01-01

Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

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Skillman, C.A.; Fletcher, H.P.

1986-01-01

The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

International Nuclear Information System (INIS)

Ai, H; Zhang, H

2014-01-01

Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

International Nuclear Information System (INIS)

Zhou, Rachel; Ng, Angela; Constine, Louis S.; Stovall, Marilyn; Armstrong, Gregory T.; Neglia, Joseph P.; Friedman, Debra L.; Kelly, Kara; FitzGerald, Thomas J.; Hodgson, David C.

2016-01-01

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

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Michael Abend

Full Text Available The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131 doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T and normal (N tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N on 64 whole genome microarrays (Agilent, 4×44 K. Associations of differential gene expression (log(2(T/N with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N. The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493 were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.

Incase of Same Region Treatment by using a Tomotherapy and a Linear Accelerator Absorbed Dose Evaluation of Normal Tissues and a Tumor

International Nuclear Information System (INIS)

Cheon, Geum Seong; Kim, Chang Uk; Kim, Hoi Nam; Heo, Gyeong Hun; Song, Jin Ho; Hong, Joo Yeong; Jeong, Jae Yong

2010-01-01

Treating same region with different modalities there is a limit to evaluate the total absorbed dose of normal tissues. The reason is that it does not support to communication each modalities yet. In this article, it evaluates absorbed dose of the patients who had been treated same region by a tomotherapy and a linear accelerator. After reconstructing anatomic structure with a anthropomorphic phantom, administrate 45 Gy to a tumor in linac plan system as well as prescribe 15 Gy in tomotherapy plan system for make an ideal treatment plan. After the plan which made by tomoplan system transfers to the oncentra plan system for reproduce plan under the same condition and realize total treatment plan with summation 45 Gy linac treatment plan. To evaluate the absorbed dose of two different modalities, do a comparative study both a simple summation dose values and integration dose values. Then compare and analyze absorbed dose of normal tissues and a tumor with the patients who had been exposured radiation by above two different modalities. The result of compared data, in case of minimum dose, there are big different dose values in spleen (12.4%). On the other hand, in case of the maximum dose, it reports big different in a small bowel (10.2%) and a cord (5.8%) in head and neck cancer patients, there presents that oral (20.3%), right lens (7.7%) in minimum dose value. About maximum dose, it represents that spinal (22.5), brain stem (12%), optic chiasm (8.9%), Rt lens (11.5%), mandible (8.1%), pituitary gland (6.2%). In case of Rt abdominal cancer patients, there represents big different minimum dose as Lt kidney (20.3%), stomach (8.1%) about pelvic cancer patients, it reports there are big different in minimum dose as a bladder (15.2%) as well as big different value in maximum dose as a small bowel (5.6%), a bladder (5.5%) in addition, making treatment plan it is able us to get. In case of comparing both simple summation absorbed dose and integration absorbed dose, the

SU-C-BRC-01: A Monte Carlo Study of Out-Of-Field Doses From Cobalt-60 Teletherapy Units Intended for Historical Correlations of Dose to Normal Tissue

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Petroccia, H [University of Florida, Gainesville, FL (United States); Olguin, E [Gainesville, FL (United States); Culberson, W [University of Wisconsin Madison, Madison, WI (United States); Bednarz, B [University of Wisconsin, Madison, WI (United States); Mendenhall, N [UF Health Proton Therapy Institute, Jacksonville, FL (United States); Bolch, W [University Florida, Gainesville, FL (United States)

2016-06-15

Purpose: Innovations in radiotherapy treatments, such as dynamic IMRT, VMAT, and SBRT/SRS, result in larger proportions of low-dose regions where normal tissues are exposed to low doses levels. Low doses of radiation have been linked to secondary cancers and cardiac toxicities. The AAPM TG Committee No.158 entitled, ‘Measurements and Calculations of Doses outside the Treatment Volume from External-Beam Radiation Therapy’, has been formed to review the dosimetry of non-target and out-of-field exposures using experimental and computational approaches. Studies on historical patients can provide comprehensive information about secondary effects from out-of-field doses when combined with long-term patient follow-up, thus providing significant insight into projecting future outcomes of patients undergoing modern-day treatments. Methods: We present a Monte Carlo model of a Theratron-1000 cobalt-60 teletherapy unit, which historically treated patients at the University of Florida, as a means of determining doses located outside the primary beam. Experimental data for a similar Theratron-1000 was obtained at the University of Wisconsin’s ADCL to benchmark the model for out-of-field dosimetry. An Exradin A12 ion chamber and TLD100 chips were used to measure doses in an extended water phantom to 60 cm outside the primary field at 5 and 10 cm depths. Results: Comparison between simulated and experimental measurements of PDDs and lateral profiles show good agreement for in-field and out-of-field doses. At 10 cm away from the edge of a 6×6, 10×10, and 20×20 cm2 field, relative out-of-field doses were measured in the range of 0.5% to 3% of the dose measured at 5 cm depth along the CAX. Conclusion: Out-of-field doses can be as high as 90 to 180 cGy assuming historical prescription doses of 30 to 60 Gy and should be considered when correlating late effects with normal tissue dose.

Options and pitfalls of normal tissues complication probability models

International Nuclear Information System (INIS)

Dorr, Wolfgang

2011-01-01

Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

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Zhou, Rachel; Ng, Angela [Department of Radiation Therapy, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Constine, Louis S. [Department of Radiation Oncology, University of Rochester, Rochester, New York (United States); Stovall, Marilyn [Division of Radiation Oncology, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Armstrong, Gregory T. [Epidemiology/Cancer Control Department, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota (United States); Friedman, Debra L. [Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Kelly, Kara [Division of Pediatric Hematology/Oncology/Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); FitzGerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Imaging and Radiation Oncology Core Group, Lincoln, Rhode Island (United States); Hodgson, David C., E-mail: David.hodgson@rmp.uhn.on.ca [Department of Radiation Oncology, University of Toronto, and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada)

2016-06-01

Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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Feng, Y [DCH Reg. Medical Center, Tuscaloosa, AL (United States)

2016-06-15

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. The margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

Science.gov (United States)

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-07

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

International Nuclear Information System (INIS)

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-01

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

International Nuclear Information System (INIS)

Moiseenko, Vitali; Battista, Jerry; Van Dyk, Jake

2000-01-01

Purpose: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. Methods and Materials: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: 'effective volume' and 'preferred Lyman'. DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. Results: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. Conclusions: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use

Local stem cell depletion model for normal tissue damage

International Nuclear Information System (INIS)

Yaes, R.J.; Keland, A.

1987-01-01

The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

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Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-01-01

Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors

International Nuclear Information System (INIS)

Keus, R.; Boer, R. de; Lebesque, J.; Noach, P.

1991-01-01

The impact of customized beam shaping was studied for 5 patients with parotid tumors treated with a paired wedged field technique. For each patient 2 plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the 2nd plan customized beam's view (BEV) designed blocks were added to both beams. The differences in those distributions between the 2 types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of un-necessary exposed normal tissue that received more than 90 percent of the prescribed dose, was reduced by a factor of about 4: from 165 to 44 percent on an average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21 percent of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4 percent (no blocks) to 4.1. percent (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for al patients when individual blocks were used. (author). 10 refs.; 4 figs.; 2 tabs

Comparison of the predictions of the LQ and CRE models for normal tissue damage due to biologically targeted radiotherapy with exponentially decaying dose rates

International Nuclear Information System (INIS)

O'Donoghue, J.A.; West of Schotland Health Boards, Glasgow

1989-01-01

For biologically targeted radiotherapy organ dose rates may be complex functions of time, related to the biodistribution kinetics of the delivery vehicle and radiolabel. The simples situation is where dose rates are exponentially decaying functions of time. Two normal tissue isoeffect models enable the effects of exponentially decaying dose rates to be addressed. These are the extension of the linear-quadratic model and the cumulative radiation effect model. This communication will compare the predictions of these models. (author). 14 refs.; 1 fig

The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

International Nuclear Information System (INIS)

Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

1988-01-01

Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells.

Science.gov (United States)

Laschinsky, Lydia; Karsch, Leonhard; Leßmann, Elisabeth; Oppelt, Melanie; Pawelke, Jörg; Richter, Christian; Schürer, Michael; Beyreuther, Elke

2016-08-01

Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells

International Nuclear Information System (INIS)

Laschinsky, Lydia; Karsch, Leonhard; Schuerer, Michael; Lessmann, Elisabeth; Beyreuther, Elke; Oppelt, Melanie; Pawelke, Joerg; Richter, Christian

2016-01-01

Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10"1"0 Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone. (orig.)

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Normal tissue complication probability for salivary glands

International Nuclear Information System (INIS)

Rana, B.S.

2008-01-01

The purpose of radiotherapy is to make a profitable balance between the morbidity (due to side effects of radiation) and cure of malignancy. To achieve this, one needs to know the relation between NTCP (normal tissue complication probability) and various treatment variables of a schedule viz. daily dose, duration of treatment, total dose and fractionation along with tissue conditions. Prospective studies require that a large number of patients be treated with varied schedule parameters and a statistically acceptable number of patients develop complications so that a true relation between NTCP and a particular variable is established. In this study Salivary Glands Complications have been considered. The cases treated in 60 Co teletherapy machine during the period 1994 to 2002 were analyzed and the clinicians judgement in ascertaining the end points was the only means of observations. The only end points were early and late xerestomia which were considered for NTCP evaluations for a period of 5 years

Dosimetry of {sup 223}Ra-chloride: dose to normal organs and tissues

Energy Technology Data Exchange (ETDEWEB)

Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nosske, Dietmar [Federal Office for Radiation Protection (BfS), Department of Radiation and Health, Oberschleissheim (Germany)

2013-02-15

{sup 223}Ra-Chloride (also called Alpharadin {sup registered}) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using {sup 223}Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of {sup 223}Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. Absorbed doses were calculated for 25 organs or tissues. Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of {sup 223}Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry. (orig.)

Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

International Nuclear Information System (INIS)

Soehn, Matthias; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

2007-01-01

Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

2012-01-01

Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

Directory of Open Access Journals (Sweden)

Bhalla NK

2006-08-01

Full Text Available Abstract Background and purpose Intensity modulated radiotherapy (IMRT is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. Materials and methods During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. Results An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. Conclusion IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs.

Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

International Nuclear Information System (INIS)

Travis, Elizabeth L.

1996-01-01

Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

Radioprotection of normal tissues of the mouse by hypoxic breathing

International Nuclear Information System (INIS)

Stevens, G.N.; Joiner, B.; Denekamp, J.

1989-01-01

Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

Directory of Open Access Journals (Sweden)

George Yang

2015-06-01

Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

Energy Technology Data Exchange (ETDEWEB)

Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

2015-05-15

Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

Review of RBE values of 15 MeV neutrons for effects on normal tissues

NARCIS (Netherlands)

Broerse, J.J.

1974-01-01

Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

International Nuclear Information System (INIS)

Pyakuryal, A; Moroz, B; Lee, C; Pelletier, C; Jung, J; Lee, C

2016-01-01

Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

Energy Technology Data Exchange (ETDEWEB)

Pyakuryal, A; Moroz, B [National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Lee, C [University of Michigan, Ann Arbor, MI (United States); Pelletier, C; Jung, J [East Carolina University Greenville, NC (United States); Lee, C [National Cancer Institute, Rockville, MD (United States)

2016-06-15

Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

Late effects of normal tissues (lent) scoring system: the soma scale

International Nuclear Information System (INIS)

Mornex, F.; Pavy, J.J.; Denekamp, J.

1997-01-01

Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

Radiation doses to normal tissues during craniospinal irradiation ...

African Journals Online (AJOL)

Mohamed Farouk Mostafa

2011-10-15

Oct 15, 2011 ... not in the center of the brain as this shows lower doses to eyes and lenses. ª 2011 Alexandria .... dose plan function was used to check the dose coverage of the .... maximum dose received by the right and left lens were listed.

The use of normal tissue complication probability to predict radiation hepatitis

International Nuclear Information System (INIS)

Keum, Ki Chang; Seong, Jin Sil; Suh, Chang Ok; Lee, Sang Wook; Chung, Eun Ji; Shin, Hyun Soo; Kim, Gwi Eon

2000-01-01

Although it has been known that the tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probability (NTCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73%, 68%) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180-200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844 (median: O.58±0.23), but that of the patients without radiation hepatitis ranged from 0.001 to 0.308 (median: 0.09±0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, volume factor of 0.32 was more

Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo

International Nuclear Information System (INIS)

Meyn, R.E.; Jenkins, W.T.

1983-01-01

The efficiency of DNA strand break formation in normal and tumor tissues of mice was measured using the technique of alkaline elution coupled with a microfluorometric determination of DNA. This methodology allowed measurement of the DNA strand breaks produced in tissues irradiated in vivo with doses of radiation comparable to those used in radiotherapy (i.e., 1.0 gray) without the necessity for the cells to be dividing and incorporating radioactive precursors to label the DNA. The results showed that substantial differences existed among various tissues in terms of the amount of DNA strand break damage produced for a given dose of radiation. Of the normal tissues, the most breaks were produced in bone marrow and the least were produced in gut. Furthermore, strand break production was relatively inefficient in the tumor compared to the normal tissues. The efficiency of DNA strand break formation measured in the cells from the tissues irradiated in vitro was much more uniform and considerably greater than that measured in vivo, suggesting that the normal tissues in the animal may be radiobiologically hypoxic

Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy

International Nuclear Information System (INIS)

Mossman, K.L.

1983-01-01

A quantitative dose-response curve for salivary gland function in patients during radiotherapy is presented. Salivary-function data used in this study were obtained from four previously published reports. All patients were treated with 60 Co teletherapy to the head and neck using conventional treatment techniques. Salivary dysfunction was determined at specific dose levels by comparing salivary flow rates before therapy with flow rates at specific dose intervals during radiotherapy up to a total dose of 6000 cGy. Fifty percent salivary dysfunction occurred after 1000 cGy and eighty percent dysfunction was observed by the end of the therapy course (6000 cGy). The salivary-function curve was also compared to the previously published dose-response curve for taste function. Comparisons of the two curves indicate that salivary dysfunction precedes taste loss and that the shapes of the dose-response curves are different. A new term, tissue tolerance ratio, defined as the ratio of responses of two tissues given the same radiation dose, was used to make the comparisons between gustatory and salivary gland tissue effects. Measurements of salivary gland function and analysis of dose-response curves may be useful in evaluating chemical modifiers of radiation response

Tumor control and normal tissue toxicity: The two faces of radiotherapy

NARCIS (Netherlands)

van Oorschot, B.

2016-01-01

This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

Large animal normal tissue tolerance with boron neutron capture.

Science.gov (United States)

Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

1994-03-30

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

Large animal normal tissue tolerance with boron neutron capture

International Nuclear Information System (INIS)

Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

1994-01-01

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

Normalized glandular dose (DgN) coefficients for flat-panel CT breast imaging

International Nuclear Information System (INIS)

Thacker, Samta C; Glick, Stephen J

2004-01-01

The development of new digital mammography techniques such as dual-energy imaging, tomosynthesis and CT breast imaging will require investigation of optimal camera design parameters and optimal imaging acquisition parameters. In optimizing these acquisition protocols and imaging systems it is important to have knowledge of the radiation dose to the breast. This study presents a methodology for estimating the normalized glandular dose to the uncompressed breast using the geometry proposed for flat-panel CT breast imaging. The simulation uses the GEANT 3 Monte Carlo code to model x-ray transport and absorption within the breast phantom. The Monte Carlo software was validated for breast dosimetry by comparing results of the normalized glandular dose (DgN) values of the compressed breast to those reported in the literature. The normalized glandular dose was then estimated for a range of breast diameters from 10 cm to 18 cm using an uncompressed breast model with a homogeneous composition of adipose and glandular tissue, and for monoenergetic x-rays from 10 keV to 120 keV. These data were fit providing expressions for the normalized glandular dose. Using these expressions for the DgN coefficients and input variables such as the diameter, height and composition of the breast phantom, the mean glandular dose for any spectra can be estimated. A computer program to provide normalized glandular dose values has been made available online. In addition, figures displaying energy deposition maps are presented to better understand the spatial distribution of dose in CT breast imaging

DNA Double-Strand Break Rejoining in Complex Normal Tissues

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

2008-01-01

Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

Low-dose computed tomography image restoration using previous normal-dose scan

International Nuclear Information System (INIS)

Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2011-01-01

Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma

International Nuclear Information System (INIS)

Yang, C.M.; Olsen, K.R.; Schwade, J.G.; Houdek, P.V.; Markoe, A.M.; Pisciotta, V.; Xiaodong Wu

1993-01-01

The dose rate effect of radiation by 125 I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plagues (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10 000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr -1 while that in ten eyes with low activity plaques was 239.9 cGy hr -1 . For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumours more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. In the second part of the experiment, 125 I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. (Author)

Radiobiology of normal tissue. Scientific advances and perspectives; Strahlenbiologie der Normalgewebe. Wissenschaftliche Fortschritte und Perspektiven

Energy Technology Data Exchange (ETDEWEB)

Doerr, W. [Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Strahlentherapie; Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Radioonkologie; Medizinische Univ. Wien (Austria). Christian Doppler Labor fuer Medizinische Strahlenforschung fuer die Radioonkologie; Herskind, C. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Labor fuer Zellulaere und Molekulare Radioonkologie

2012-11-15

Radiotherapy involves always the exposure of normal tissue, resulting in an excepted risk of complications. The side effect rate is therefore the compromise between optimized tumor doses and the side effect minimization. The report covers the issues target cell hypothesis and the consequences, new aspect of the pathogenesis of normal issue reactions and strategies of targeted reduction of normal tissue effects. The complexity of the radiobiological processes, the specificity and action mechanisms, the mutual interactions of chemical and radiological processes require further coordinated radiobiological research in the future.

Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

International Nuclear Information System (INIS)

Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

2006-01-01

Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

Mathematical models of tumour and normal tissue response

International Nuclear Information System (INIS)

Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

1999-01-01

The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

Energy Technology Data Exchange (ETDEWEB)

Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2014-06-01

Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

Selectivity of Very High Dose Methotrexate in Mcf-7 and Normal Cells Using a Priming and Non-Toxic 5-Fluorouracil Dose

National Research Council Canada - National Science Library

Brown, Donnell

1997-01-01

...) in MCF-7 breast cancer cells versus normal tissues and (b) provide one clear basis for intracellular rescue of only host cells from MTX toxicity when high dose MTX is used in combination with 5-fluorouracil (5-FU...

The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy

International Nuclear Information System (INIS)

Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul; Petersen, Joergen B.

2009-01-01

We have implemented an intensity-modulated radiotherapy (IMRT) protocol for simultaneous irradiation of bladder and lymph nodes. In this report, doses to normal tissue from IMRT and our previous conformal sequential boost technique are compared. Material and methods. Sixteen patients with urinary bladder cancer were treated using a six-field dynamic IMRT beam arrangement delivering 60 Gy to the bladder and 48 Gy to the pelvic lymph nodes. Dose-volume histogram (DVH) parameters for relevant normal tissues (bowel, bowel cavity, rectum and femoral heads) for the IMRT plans were compared with corresponding DVHs from our previous conformal sequential boost technique. Calculations of the generalized Equivalent Uniform Dose (gEUD) were performed for the bowel, with a reference volume of 200 cm 3 and a volume effect parameter k = 4, as well as for the rectum, using k = 12. Acute gastrointestinal (GI) and genitourinary (GU) RTOG toxicity was recorded. Results. Statistical significant normal tissue sparing was obtained by IMRT. For the bowel, a significant reduction was obtained at all dose levels between 20 and 50 Gy (p 3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p 3 at 50 Gy. The rectum gEUD was reduced from 55 to 53 Gy (p < 0.05). For the femoral heads, IMRT reduced the maximum dose as well as the volumes above all dose levels. The rate of acute peak Grade 2 GI RTOG complications was 38% after IMRT. Conclusion. IMRT to the urinary bladder and elective lymph nodes result in considerable normal tissue sparing compared to conformal sequential boost technique. This has paved the way for further studies combining IMRT with image-guided radiotherapy (IGRT) in bladder cancer

A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

2010-01-01

Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin...... B(3)). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg....../kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified...

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

International Nuclear Information System (INIS)

Constine, L; Hodgson, D; Bentzen, S

2014-01-01

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

Energy Technology Data Exchange (ETDEWEB)

Constine, L; Hodgson, D; Bentzen, S [University of Maryland, Baltimore, MD (United States)

2014-06-15

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

Radiation doses to normal tissues during craniospinal irradiation ...

African Journals Online (AJOL)

Objective: This dosimetric study is aiming to report the results of the analysis of doses received by target volumes and organs outside the target volumes during the treatment of medulloblastoma patients. And also by comparing the doses reaching the eyes and the lens with the use of different shielding methods.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

2014-09-15

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

International Nuclear Information System (INIS)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

2014-01-01

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Impact of margin on tumour and normal tissue dosimetry in patients treated with IMRT using an endorectal balloon for prostate immobilization

International Nuclear Information System (INIS)

Ahmad, S.

2004-01-01

Full text: In treatment of prostate cancer with IMRT (Intensity Modulated Radiation Therapy), clinical target volume margin is determined by organ motion and set-up error. However, the margin width that achieves the desired dose escalation while minimizing normal tissue exposure is dependent upon the patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using the endorectal balloon for prostate immobilization. IMRT plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. Patients had a planning CT scan in the prone position with an endorectal balloon filled with 100 cc of air for prostate immobilization. The Corvus version 3.0.11 was used for treatment planning. The dose for the prostate and seminal vesicles was 70 Gy in 2 Gy per fractions, prescribed at the 83% isodose line. Dose restrictions to normal tissues were as follows: 33% of bladder was allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Analysis of Variance was used to compare the target and normal tissue doses. Tumour control probability and normal tissue complication probability calculations are currently being performed and will be presented. The mean doses ranged from 73.93 to 75.31 Gy for the prostate and from 73.71 to 75.31 Gy for the seminal vesicles. A 10 mm margin produced significantly lower mean doses compared to 0 or 5 mm for both targets (prostate p 0.062). For bladder and rectum the mean doses ranged from 18.49 to 22.30 Gy (p=0.605) and from 29.34 to 31.33 Gy (p=0.135), respectively, while the percent rectal volumes above 68 Gy were significantly higher for margins of 5, 8 and 10 mm (p<0.006) ranging from 10.72% to 15.81%. Mean doses to the femurs and pelvis were significantly higher for 8 and 10 mm margins, ranging from 20.9 to 29.39 Gy for femurs (p<0.015) and from 15.05 to 19.98 Gy for pelvis (p<0.0005). Also the percent

Dose in water or dose in tissue. Still a theme of debate; Dosis en agua o dosis en tejido-todavia un tema de debate

Energy Technology Data Exchange (ETDEWEB)

Andreo, P.

2015-07-01

It is shown that the method used so Siebers to convert to Dw Dt, or vice versa, is incorrect. Due to the substantial difference between the electron fluence in water and various tissues, an additional correction for creep, several percent for some bone tissues, which is ignored in the method Siebers needed. Correction is necessary even if an environment that clinically adopted dose in tissue due to normalization of TPS because the beams are always calibrated in terms of absorbed dose in water. (Author)

Radioprotection of normal tissues in tumor-bearing mice by troxerutin

International Nuclear Information System (INIS)

Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

2004-01-01

The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

Organ or tissue doses, effective dose and collective effective dose from X-ray diagnosis, in Japan

International Nuclear Information System (INIS)

Murayama, Takashi; Nishizawa, Kanae; Noda, Yutaka; Kumamoto, Yoshikazu; Iwai, Kazuo.

1996-01-01

Effective doses and collective effective doses from X-ray diagnostic examinations were calculated on the basis of the frequency of examinations estimated by a nationwide survey and the organ or tissue doses experimentally determined. The average organ or tissue doses were determined with thermoluminescence dosimeters put at various sites of organs or tissues in an adult and a child phantom. Effective doses (effective dose equivalents) were calculated as the sum of the weighted equivalent doses in all the organs or tissues of the body. As the examples of results, the effective doses per radiographic examination were approximately 7 mGy for male, and 9 mGy for female angiocardiography, and about 3 mGy for barium meal. Annual collective effective dose from X-ray diagnostic examinations in 1986 were about 104 x 10 3 person Sv from radiography and 118 x 10 3 person Sv from fluoroscopy, with the total of 222 x 10 3 person Sv. (author)

Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

International Nuclear Information System (INIS)

Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

2011-01-01

Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

Integral dose conservation in radiotherapy

International Nuclear Information System (INIS)

Reese, Adam S.; Das, Shiva K.; Curle, Charles; Marks, Lawrence B.

2009-01-01

Treatment planners frequently modify beam arrangements and use IMRT to improve target dose coverage while satisfying dose constraints on normal tissues. The authors herein analyze the limitations of these strategies and quantitatively assess the extent to which dose can be redistributed within the patient volume. Specifically, the authors hypothesize that (1) the normalized integral dose is constant across concentric shells of normal tissue surrounding the target (normalized to the average integral shell dose), (2) the normalized integral shell dose is constant across plans with different numbers and orientations of beams, and (3) the normalized integral shell dose is constant across plans when reducing the dose to a critical structure. Using the images of seven patients previously irradiated for cancer of brain or prostate cancer and one idealized scenario, competing three-dimensional conformal and IMRT plans were generated using different beam configurations. Within a given plan and for competing plans with a constant mean target dose, the normalized integral doses within concentric ''shells'' of surrounding normal tissue were quantitatively compared. Within each patient, the normalized integral dose to shells of normal tissue surrounding the target was relatively constant (1). Similarly, for each clinical scenario, the normalized integral dose for a given shell was also relatively constant regardless of the number and orientation of beams (2) or degree of sparing of a critical structure (3). 3D and IMRT planning tools can redistribute, rather than eliminate dose to the surrounding normal tissues (intuitively known by planners). More specifically, dose cannot be moved between shells surrounding the target but only within a shell. This implies that there are limitations in the extent to which a critical structure can be spared based on the location and geometry of the critical structure relative to the target.

Tissue dose in thorotrast patients

International Nuclear Information System (INIS)

Kaul, A.; Noffz, W.

1978-01-01

Absorbed doses to the liver, spleen, red marrow, lungs, kidneys, and to various parts of bone tissue were calculated for long-term burdens of intravascularly injected Thorotrast. The estimates were performed for typical injection levels of 10, 30, 50 and 100 ml, based upon best estimates of 232 Th tissue distribution, and steady state activity ratios between the subsequent daughters. Correcting for the α-particle self absorption within Thorotrast aggregates, the mean α-dose to a standard 70-kg man at 30 yr after the injection 0f 25 ml of Thorotrast is 750 rad to the liver, 2100 rad to the spleen, 270 rad to the red marrow, 60-620 rad in various parts of the lung, and 13 rad to the kidneys. Dose rates to various parts of bone tissue (bone surface, compact, and cancellous bone) were estimated by applying the ICRP model on alkaline earth metabolism to the continuous translocation of thorium daughters to bone and to the formation of thorium daughters by decay within bone tissue. The average dose to calcified bone from translocated 224 Ra with its daughters is 18 rad at 30 yr after the injection of 25 ml of Thorotrast. Considering the Spiess-Mays risk coefficient of 0.9-1.7% bone sarcoma/ 100 rad of average skeletal dose from 224 Ra and its daughters, the induction of 1.6-3.1 bone sarcomas per 1000 Thorotrast patients is predicted. (author)

Mathematical model of normal tissue injury in telegammatherapy

International Nuclear Information System (INIS)

Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

1983-01-01

A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: Does IMRT increase the integral dose to normal brain?

International Nuclear Information System (INIS)

Hermanto, Ulrich; Frija, Erik K.; Lii, MingFwu J.; Chang, Eric L.; Mahajan, Anita; Woo, Shiao Y.

2007-01-01

Purpose: To determine whether intensity-modulated radiotherapy (IMRT) treatment increases the total integral dose of nontarget tissue relative to the conventional three-dimensional conformal radiotherapy (3D-CRT) technique for high-grade gliomas. Methods and Materials: Twenty patients treated with 3D-CRT for glioblastoma multiforme were selected for a comparative dosimetric evaluation with IMRT. Original target volumes, organs at risk (OAR), and dose-volume constraints were used for replanning with IMRT. Predicted isodose distributions, cumulative dose-volume histograms of target volumes and OAR, normal tissue integral dose, target coverage, dose conformity, and normal tissue sparing with 3D-CRT and IMRT planning were compared. Statistical analyses were performed to determine differences. Results: In all 20 patients, IMRT maintained equivalent target coverage, improved target conformity (conformity index [CI] 95% 1.52 vs. 1.38, p mean by 19.8% and D max by 10.7%), optic chiasm (D mean by 25.3% and D max by 22.6%), right optic nerve (D mean by 37.3% and D max by 28.5%), and left optic nerve (D mean by 40.6% and D max by 36.7%), p ≤ 0.01. This was achieved without increasing the total nontarget integral dose by greater than 0.5%. Overall, total integral dose was reduced by 7-10% with IMRT, p < 0.001, without significantly increasing the 0.5-5 Gy low-dose volume. Conclusions: These results indicate that IMRT treatment for high-grade gliomas allows for improved target conformity, better critical tissue sparing, and importantly does so without increasing integral dose and the volume of normal tissue exposed to low doses of radiation

EPR study of the reactions of tumour and normal tissues under ionizing radiation

International Nuclear Information System (INIS)

Rikhireva, G.T.; Pulatova, M.K.; Turganov, M.M.; Pal'mina, N.P.; Burlakova, E.B.

1978-01-01

Data on the EPR spectrum characteristics of irradiated tissues of tumour-free animals and animals with tumour are presented. Mice of the Csub(3)Hsub(A) line were used in the experiments. Hepatoma was subcutaneously transplanted with the suspension of tumour tissue reduced to fragments. Animals were killed in 6-8 days after transplantation and in the case of tumour-free animals liver was immediately isolated while in the case of animals with tumour isolated were liver and tumour. Tissues cut with scissors were frozen in liquid nitrogen. Tissue samples were exposed to 60 Co at 1 Mrad dose and -196 deg C. On the base of the data it has been concluded: firstly, there are differences between the EPR spectra of normal and tumour tissue samples irradiated at -196 deg C. Asymmetryc signal with Δ H=Ge and g=2.0005 (''tumour signal'') is typical only for the EPR spectra of tumour and liver tissues of the animal with tumour. Thus, in the -author's opinion, irradiation use turns out to be useful for detecting the difference between the normal and tumour tissues. Secondly, ''tumour signal'' intensity changes after ionol incorporation into animal organism, used as a modificator of tissue sensitivity to the irradiation effect

SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

Energy Technology Data Exchange (ETDEWEB)

Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

2014-06-01

Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer

International Nuclear Information System (INIS)

Manning, Matthew A.; Wu Quiwen; Cardinale, Robert M.; Mohan, Radhe; Lauve, Andrew D.; Kavanagh, Brian D.; Morris, Monica M.; Schmidt-Ullrich, Rupert K.

2001-01-01

Purpose: Intensity-modulated radiotherapy (IMRT) is being evaluated in the management of head-and-neck cancers at several institutions, and a Radiation Therapy Oncology Group study of its utility in parotid sparing is under development. There is an inherent risk that the sharper dose gradients generated by IMRT amplify the potentially detrimental impact of setup uncertainty. The International Commission on Radiation Units and Measurements Report 62 (ICRU-62) defined planning organ-at-risk volume (PRV) to account for positional uncertainties for normal tissues. The purpose of this study is to quantify the dosimetric effect of employing PRV for the parotid gland and to evaluate the use of PRV on normal-tissue sparing in the setting of small clinical setup errors. Methods and Materials: The optimized nine-beam IMRT plans for three head-and-neck cancer patients participating in an institutional review board approved parotid-sparing protocol were used as reference plans. A second optimized plan was generated for each patient by adding a PRV of 5 mm for the contralateral parotid gland. The effect of these additions on the quality of the plans was quantified, in terms of both target coverage and normal-tissue sparing. To test the value of PRV in a worst-case scenario, systematic translational setup uncertainties were simulated by shifting the treatment isocenter 5 mm superiorly, inferiorly, left, right, anteriorly, and posteriorly, without altering optimized beam profiles. At each shifted isocenter, dose distributions were recalculated, producing a total of six shifted plans without PRV and six shifted plans with PRV for each patient. The effect of setup uncertainty on parotid sparing and the value of PRV in compensating for the uncertainty were evaluated. Results: The addition of the PRV and reoptimization did not significantly affect the dose to gross tumor volume, spinal cord, or brainstem. In contrast, without any shift, the PRV did increase parotid sparing and reduce

CURED I - LENT. Late effects of cancer treatment on normal tissues

International Nuclear Information System (INIS)

Rubin, P.; Okunieff, P.; Constine, L.S.; Rochester Univ. School of Medicine and Dentistry, Rochester, NY; Marks, L.B.

2008-01-01

The search for the most favorable therapeutic ratio - at which ablation of cancer is achieved while normal tissues are conserved - has been modern radiation oncology's equivalent of the quest for the Holy Grail. Our awareness of the late effects of radiation grew during the past century as new modalities were introduced. Heightened normal tissue reactions accompanied the higher rates of cancer ablation achieved by escalation of radiation doses, accelerated fractionated radiotherapy, and aggressive concurrent chemotherapy and radiation regimens. This volume is based on the LENT V NCI-sponsored meeting held in May 2004 and the CURED I conference held in 2006. Written by experts in the field, it addresses a number of critical topics relating to late effects, such as mechanisms of injury, the role of screening, options for interventions, second malignancies, and prevention. It is hoped that it will assist the reader in understanding how to prevent and treat the long-term side-effects of irradiation. (orig.)

Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

International Nuclear Information System (INIS)

Zhang, H.; Wheeler, K.T.

1994-01-01

Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

SU-D-16A-01: A Novel Method to Estimate Normal Tissue Dose for Radiotherapy Patients to Support Epidemiologic Studies of Second Cancer Risk

Energy Technology Data Exchange (ETDEWEB)

Lee, C [University of Michigan, Ann Arbor, MI (United States); Jung, J; Pelletier, C [East Carolina University, Greenville, NC (United States); Kim, J [University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lee, C [National Cancer Institute, Bethesda, MD (United States)

2014-06-01

Purpose: Patient cohort of second cancer study often involves radiotherapy patients with no radiological images available: We developed methods to construct a realistic surrogate anatomy by using computational human phantoms. We tested this phantom images both in a commercial treatment planning system (Eclipse) and a custom Monte Carlo (MC) transport code. Methods: We used a reference adult male phantom defined by International Commission on Radiological Protection (ICRP). The hybrid phantom which was originally developed in Non-Uniform Rational B-Spline (NURBS) and polygon mesh format was converted into more common medical imaging format. Electron density was calculated from the material composition of the organs and tissues and then converted into DICOM format. The DICOM images were imported into the Eclipse system for treatment planning, and then the resulting DICOM-RT files were imported into the MC code for MC-based dose calculation. Normal tissue doses were calculation in Eclipse and MC code for an illustrative prostate treatment case and compared to each other. Results: DICOM images were generated from the adult male reference phantom. Densities and volumes of selected organs between the original phantom and ones represented within Eclipse showed good agreements, less than 0.6%. Mean dose from Eclipse and MC code match less than 7%, whereas maximum and minimum doses were different up to 45%. Conclusion: The methods established in this study will be useful for the reconstruction of organ dose to support epidemiological studies of second cancer in cancer survivors treated by radiotherapy. We also work on implementing body size-dependent computational phantoms to better represent patient's anatomy when the height and weight of patients are available.

Optimization of stereotactically-guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms

International Nuclear Information System (INIS)

Perks, Julian R.; Jalali, Rakesh; Cosgrove, Vivian P.; Adams, Elizabeth J.; Shepherd, Stephen F.; Warrington, Alan P.; Brada, Michael

1999-01-01

Purpose: To investigate the optimal treatment plan for stereo tactically-guided conformal radiotherapy (SCRT) of sellar and parasellar lesions, with respect to sparing normal brain tissue, in the context of routine treatment delivery, based on dose volume histogram analysis. Methods and Materials: Computed tomography (CT) data sets for 8 patients with sellar- and parasellar-based tumors (6 pituitary adenomas and 2 meningiomas) have been used in this study. Treatment plans were prepared for 3-coplanar and 3-, 4-, 6-, and 30-noncoplanar-field arrangements to obtain 95% isodose coverage of the planning target volume (PTV) for each plan. Conformal shaping was achieved by customized blocks generated with the beams eye view (BEV) facility. Dose volume histograms (DVH) were calculated for the normal brain (excluding the PTV), and comparisons made for normal tissue sparing for all treatment plans at ≥80%, ≥60%, and ≥40% of the prescribed dose. Results: The mean volume of normal brain receiving ≥80% and ≥60% of the prescribed dose decreased by 22.3% (range 14.8-35.1%, standard deviation σ = 7.5%) and 47.6% (range 25.8-69.1%, σ 13.2%), respectively, with a 4-field noncoplanar technique when compared with a conventional 3-field coplanar technique. Adding 2 further fields, from 4-noncoplanar to 6-noncoplanar fields reduced the mean normal brain volume receiving ≥80% of the prescribed dose by a further 4.1% (range -6.5-11.8%, σ = 6.4%), and the volume receiving ≥60% by 3.3% (range -5.5-12.2%, σ = 5.4%), neither of which were statistically significant. Each case must be considered individually however, as a wide range is seen in the volume spared when increasing the number of fields from 4 to 6. Comparing the 4- and 6-field noncoplanar techniques to a 30-field conformal field approach (simulating a dynamic arc plan) revealed near-equivalent normal tissue sparing. Conclusion: Four to six widely spaced, fixed-conformal fields provide the optimum class solution

Oxygen delivery in irradiated normal tissue

Energy Technology Data Exchange (ETDEWEB)

Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

2003-03-01

Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

Brachytherapy dose measurements in heterogeneous tissues

International Nuclear Information System (INIS)

Paiva F, G.; Luvizotto, J.; Salles C, T.; Guimaraes A, P. C.; Dalledone S, P. de T.; Yoriyaz, H.; Rubo, R.

2014-08-01

Recently, Beau lieu et al. published an article providing guidance for Model-Based Dose Calculation Algorithms (MBDCAs), where tissue heterogeneity considerations are addressed. It is well-known that T G-43 formalism which considers only water medium is limited and significant dose differences have been found comparing both methodologies. The aim of the present work is to experimentally quantify dose values in heterogeneous medium using different dose measurement methods and techniques and compare them with those obtained with Monte Carlo simulations. Experiments have been performed using a Nucletron micro Selectron-Hdr Ir-192 brachytherapy source and a heterogeneous phantom composed by PMMA and different tissue equivalent cylinders like bone, lungs and muscle. Several dose measurements were obtained using tissue equivalent materials with height 1.8 cm and 4.3 cm positioned between the radiation source and the detectors. Radiochromic films, TLDs and MOSFET S have been used for the dose measurements. Film dosimetry has been performed using two methodologies: a) linearization for dose-response curve based on calibration curves to create a functional form that linearize s the dose response and b) 177 multichannel analysis dosimetry where the multiple color channels are analyzed allowing to address not only disturbances in the measurements caused by thickness variation in the film layer, but also, separate other external influences in the film response. All experiments have been simulated using the MCNP5 Monte Carlo radiation transport code. Comparison of experimental results are in good agreement with calculated dose values with differences less than 6% for almost all cases. (Author)

Brachytherapy dose measurements in heterogeneous tissues

Energy Technology Data Exchange (ETDEWEB)

Paiva F, G.; Luvizotto, J.; Salles C, T.; Guimaraes A, P. C.; Dalledone S, P. de T.; Yoriyaz, H. [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil); Rubo, R., E-mail: gabrielpaivafonseca@gmail.com [Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo (Brazil)

2014-08-15

Recently, Beau lieu et al. published an article providing guidance for Model-Based Dose Calculation Algorithms (MBDCAs), where tissue heterogeneity considerations are addressed. It is well-known that T G-43 formalism which considers only water medium is limited and significant dose differences have been found comparing both methodologies. The aim of the present work is to experimentally quantify dose values in heterogeneous medium using different dose measurement methods and techniques and compare them with those obtained with Monte Carlo simulations. Experiments have been performed using a Nucletron micro Selectron-Hdr Ir-192 brachytherapy source and a heterogeneous phantom composed by PMMA and different tissue equivalent cylinders like bone, lungs and muscle. Several dose measurements were obtained using tissue equivalent materials with height 1.8 cm and 4.3 cm positioned between the radiation source and the detectors. Radiochromic films, TLDs and MOSFET S have been used for the dose measurements. Film dosimetry has been performed using two methodologies: a) linearization for dose-response curve based on calibration curves to create a functional form that linearize s the dose response and b) 177 multichannel analysis dosimetry where the multiple color channels are analyzed allowing to address not only disturbances in the measurements caused by thickness variation in the film layer, but also, separate other external influences in the film response. All experiments have been simulated using the MCNP5 Monte Carlo radiation transport code. Comparison of experimental results are in good agreement with calculated dose values with differences less than 6% for almost all cases. (Author)

Radiogenomics: predicting clinical normal tissue radiosensitivity

DEFF Research Database (Denmark)

Alsner, Jan

2006-01-01

Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

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Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy

International Nuclear Information System (INIS)

Dale, Einar; Olsen, Dag R.; Fossa, Sophie D.

1999-01-01

Purpose: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. Methods and Materials: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. Results: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p max , of the whole rectum, correlated better to observed late toxicity than D max derived from histograms of the rectum wall. Correlation coefficients from 'high-dose' measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p < 0.01 level. Conclusions: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late

A compendium of canine normal tissue gene expression.

Directory of Open Access Journals (Sweden)

Joseph Briggs

Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

DNA-repair, cell killing and normal tissue damage

International Nuclear Information System (INIS)

Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

1998-01-01

Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

Energy Technology Data Exchange (ETDEWEB)

Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen; Lee, Jae; Lee, Choonik; Matuszak, Martha M.; Ten Haken, Randall K.; Brock, Kristy K., E-mail: kbrock@med.umich.edu

2016-11-01

Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the

Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

2010-01-01

Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

Radiation-induced normal tissue damage: implications for radiotherapy

International Nuclear Information System (INIS)

Prasanna, Pataje G.

2014-01-01

Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

Science.gov (United States)

Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

2010-03-01

Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom

International Nuclear Information System (INIS)

Company, F.Z.; Allen, B.J.

1998-01-01

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20x20cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings. (author)

Canine tumor and normal tissue response to heat and radiation

International Nuclear Information System (INIS)

Gillette, E.L.; McChesney, S.L.

1985-01-01

Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

High-dose erythropoietin for tissue protection

DEFF Research Database (Denmark)

Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

2014-01-01

BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

International Nuclear Information System (INIS)

Koh, Eng-Siew; Paul, Narinder; Hodgson, David C; Tran, Tu Huan; Heydarian, Mostafa; Sachs, Rainer K; Tsang, Richard W; Brenner, David J; Pintilie, Melania; Xu, Tony; Chung, June

2007-01-01

Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

The efficacy of hyperbaric oxygen in modifying the response of tissue to irradiation in doses of 200-400 rad per fraction

International Nuclear Information System (INIS)

Suit, D.D.; Orsi, L.

1975-01-01

The efficacy of respiration of O 2 at 30 psi in modifying the response of normal and tumour tissue to irradiation administered at 200 to 400 rad per fraction to anaesthetized mice has been evaluated. End-points have been delay in growth and TCD 50 for an early generation iso-transplant of a C 3 H mouse mammary carcinoma, and the acute reaction of skin of the C 3 H/Sed mouse. Results showed that the ratios of dose (air)/dose (O 2 30 psi) to elicit these end points were in the range 1.2 to 1.4. In earlier work using the same end points but doses per fraction 430 to 2100 rad, the ratios were 1.6 to 1.8. That is, for these tissue responses, respiration of O 2 at 30 psi increases the response of both normal and tumour tissue to all radiation doses tested. It is of greater effectiveness when combined with large doses per fraction, eg. greater than 430 rad. (author)

Telomere length in normal and neoplastic canine tissues.

Science.gov (United States)

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Pathologic evaluation of normal and perfused term placental tissue

DEFF Research Database (Denmark)

Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

2014-01-01

This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

SU-E-J-264: Using Magnetic Resonance Imaging-Derived Features to Quantify Radiotherapy-Induced Normal Tissue Morbidity

Energy Technology Data Exchange (ETDEWEB)

Thor, M; Tyagi, N; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

2015-06-15

Purpose: The aim of this study was to explore the use of Magnetic Resonance Imaging (MRI)-derived features as indicators of Radiotherapy (RT)-induced normal tissue morbidity. We also investigate the relationship between these features and RT dose in four critical structures. Methods: We demonstrate our approach for four patients treated with RT for base of tongue cancer in 2005–2007. For each patient, two MRI scans (T1-weighted pre (T1pre) and post (T1post) gadolinium contrast-enhancement) were acquired within the first six months after RT. The assessed morbidity endpoint observed in 2/4 patients was Grade 2+ CTCAEv.3 trismus. Four ipsilateral masticatory-related structures (masseter, lateral and medial pterygoid, and the temporal muscles) were delineated on both T1pre and T1post and these scans were co-registered to the treatment planning CT using a deformable demons algorithm. For each structure, the maximum and mean RT dose, and six MRI-derived features (the second order texture features entropy and homogeneity, and the first order mean, median, kurtosis, and skewness) were extracted and compared structure-wise between patients with and without trismus. All MRI-derived features were calculated as the difference between T1pre and T1post, ΔS. Results: For 5/6 features and all structures, ΔS diverged between trismus and non-trismus patients particularly for the masseter, lateral pterygoid, and temporal muscles using the kurtosis feature (−0.2 vs. 6.4 for lateral pterygoid). Both the maximum and mean RT dose in all four muscles were higher amongst the trismus patients (with the maximum dose being up to 25 Gy higher). Conclusion: Using MRI-derived features to quantify RT-induced normal tissue complications is feasible. We showed that several features are different between patients with and without morbidity and that the RT dose in all investigated structures are higher amongst patients with morbidity. MRI-derived features, therefore, has the potential to

Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

Directory of Open Access Journals (Sweden)

Annika eJakobi

2015-11-01

Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

Dose-specific transcriptional responses in thyroid tissue in mice after 131I administration

International Nuclear Information System (INIS)

Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2015-01-01

Introduction: In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after 131 I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with 131 I exposure in normal mouse thyroid tissue and 2) propose biomarkers for 131 I exposure of the thyroid. Methods: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of 131 I and killed 24 h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. Results: In total, 497, 546, and 90 transcripts were regulated (fold change ≥ 1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Conclusion: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to 131 I exposure of thyroid. Advances in knowledge: During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

Energy Technology Data Exchange (ETDEWEB)

Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian [Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, New South Wales (Australia)

2015-09-15

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

International Nuclear Information System (INIS)

Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

2015-01-01

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT

Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

International Nuclear Information System (INIS)

Abderrahmani, R.

2010-01-01

Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice

International Nuclear Information System (INIS)

Swailem, Fayez M.; Krishnamurthy, Gerbail T.; Srivastava, Suresh C.; Aguirre, Maria L.; Ellerson, Dawn L.; Walsh, T. Kent; Simpson, Laura

1998-01-01

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a γ-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. γ-Ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogenous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected

Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

Science.gov (United States)

Bakhshandeh, Mohsen; Hashemi, Bijan; Mahdavi, Seied Rabi Mehdi; Nikoofar, Alireza; Vasheghani, Maryam; Kazemnejad, Anoshirvan

2013-02-01

To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the

Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Bakhshandeh, Mohsen [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Mahdavi, Seied Rabi Mehdi [Department of Medical Physics, Faculty of Medical Sciences, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Nikoofar, Alireza; Vasheghani, Maryam [Department of Radiation Oncology, Hafte-Tir Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kazemnejad, Anoshirvan [Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

2013-02-01

Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

International Nuclear Information System (INIS)

Turesson, I.

1990-01-01

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

Neutron organ dose and the influence of adipose tissue

Science.gov (United States)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

Integral dose and evaluation of irradiated tissue volume

International Nuclear Information System (INIS)

Sivachenko, T.P.; Kalina, V.K.; Belous, A.K.; Gaevskij, V.I.

1984-01-01

Two parameters having potentialities of radiotherapy planning improvement are under consideration. One of these two parameters in an integral dose. An efficiency of application of special tables for integral dose estimation is noted. These tables were developed by the Kiev Physician Improvement Institute and the Cybernetics Institute of the Ukrainian SSR Academy of Science. The meaning of the term of ''irradiated tissue volume'' is specified, and the method of calculation of the irradiated tissue effective mass is considered. It is possible to evaluate with higher accuracy tolerance doses taking into account the irradiated mass

Tolerance doses of cutaneous and mucosal tissues in ring-necked parakeets (Psittacula krameri) for external beam megavoltage radiation.

Science.gov (United States)

Barron, Heather W; Roberts, Royce E; Latimer, Kenneth S; Hernandez-Divers, Stephen; Northrup, Nicole C

2009-03-01

Currently used dosages for external-beam megavoltage radiation therapy in birds have been extrapolated from mammalian patients and often appear to provide inadequate doses of radiation for effective tumor control. To determine the tolerance doses of cutaneous and mucosal tissues of normal birds in order to provide more effective radiation treatment for tumors that have been shown to be radiation responsive in other species, ingluvial mucosa and the skin over the ingluvies of 9 ring-necked parakeets (Psittacula krameri) were irradiated in 4-Gy fractions to a total dose of either 48, 60, or 72 Gy using an isocentric cobalt-60 teletherapy unit. Minimal radiation-induced epidermal changes were present in the high-dose group histologically. Neither dose-related acute nor chronic radiation effects could be detected in any group grossly in cutaneous or mucosal tissue over a 9-month period. Radiation doses of 72 Gy in 4-Gy fractions were well tolerated in the small number of ring-necked parakeets in this initial tolerance dose study.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

International Nuclear Information System (INIS)

Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Radiation Dose Estimates in Indian Adults in Normal and Pathological Conditions due to 99Tcm-Labelled Radiopharmaceuticals

International Nuclear Information System (INIS)

Tyagi, K.; Jain, S.C.; Jain, P.C.

2001-01-01

ICRP Publications 53, 62 and 80 give organ dose coefficients and effective doses to ICRP Reference Man and Child from established nuclear medicine procedures. However, an average Indian adult differs significantly from the ICRP Reference Man as regards anatomical, physiological and metabolic characteristics, and is also considered to have different tissue weighting factors (called here risk factors). The masses of total body and most organs are significantly lower for the Indian adult than for his ICRP counterpart (e.g. body mass 52 and 70 kg respectively). Similarly, the risk factors are lower by 20-30% for 8 out of the 13 organs and 30-60% higher for 3 organs. In the present study, available anatomical data of Indians and their risk factors have been utilised to estimate the radiation doses from administration of commonly used 99 Tc m -labelled radiopharmaceuticals under normal and certain pathological conditions. The following pathological conditions have been considered for phosphates/phosphonates - high bone uptake and severely impaired kidney function; IDA - parenchymal liver disease, occlusion of cystic duct, and occlusion of bile duct; DTPA - abnormal renal function; large colloids - early to intermediate diffuse parenchymal liver disease, intermediate to advanced parenchymal liver disease; small colloids - early to intermediate parenchymal liver disease, intermediate to advanced parenchymal liver disease; and MAG3 - abnormal renal function, acute unilateral renal blockage. The estimated 'effective doses' to Indian adults are 14-21% greater than the ICRP value from administration of the same activity of radiopharmaceutical under normal physiological conditions based on anatomical considerations alone, because of the smaller organ masses for the Indian; for some pathological conditions the effective doses are 11-22% more. When tissue risk factors are considered in addition to anatomical considerations, the estimated effective doses are still found to be

Iso-effect tables for tolerance of irradiated normal human tissues

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

Available literature on a radiation injury to human tissues (lung, brain, kidney and intestine) was surveyed. A parameter search program (RAD3) was used to derive best-fitting cell kinetic parameters, on the assumption that radiation injury arises from depletion of parenchymal cells in the irradiated organs. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals, for each tissue. The tables provide a set of limiting doses, above which the risk of radiation injury becomes substantial. Tolerance limits and dose-time-factors were substantially different in the four tissues. It is concluded that computed iso-effect tables provide a more reliable guide to treatment than conventional time-dose equations

Risk assessment from heterogeneous energy deposition in tissue, the problem of effects from low doses of ionizing radiation

International Nuclear Information System (INIS)

Feinendegen, L.E.; Booz, J.

1992-01-01

Low doses of ionizing radiation from external or internal sources cause heterogeneous distribution of energy deposition events in the exposed biological system. With the cell being the individual element of the tissue system, the fraction of cells hit, the dose received by the hit, and the biological response of the cell to the dose received eventually determine the effect in tissue. The hit cell may experience detriment, such as change in its DNA leading to a malignant transformation, or it may derive benefit in terms of an adaptive response such as a temporary improvement of DNA repair or temporary prevention of effects from intracellular radicals through enhanced radical detoxification. These responses are protective also to toxic substances that are generated during normal metabolism. Within a multicellular system the probability of detriment must be weighed against the probability of benefit through adaptive responses with protection against various toxic agents including those produced by normal metabolism. Because irradiation can principally induce both, detriment and adaptive responses, one type of affected cells may not be simply summed up at the expense of cells with other types of effects, in assessing risk to tissue. An inventory of various types of effects in the blood-forming system of mammals, even with large ranges of uncertainty, uncovers the possibility of benefit to the system from exposure to low doses of low-LET radiation. This experimental approach may complement epidemiological data on individuals exposed to low doses of ionizing radiation and may lead to a more rational appraisal of risk

Investigation of normal tissue complication probabilities in prostate and partial breast irradiation radiotherapy techniques

International Nuclear Information System (INIS)

Bezak, E.; Takam, R.; Bensaleh, S.; Yeoh, E.; Marcu, L.

2011-01-01

Full text: Normal- Tissue-Complication Probabilities of rectum, bladder and urethra following various radiation techniques for prostate cancer were evaluated using the relative-seriality and Lyman models. NTCPs of lungs, heart and skin, their dependence on sourceposition, balloon-deformation were also investigated for HDR mammosite brachytherapy. The prostate treatment techniques included external three dimentional conformal-radiotherapy, Low-Dose-Rate brachytherapy (1-125), High-Dose-Rate brachytherapy (Ir-I92). Dose- Volume-Histograms of critical structures for prostate and breast radiotherapy, retrieved from corresponding treatment planning systems, were converted to Biological Effective Dose (BEffD)-based and Equivalent Dose(Deq)-based DVHs to account for differences in radiation delivery and fractionation schedule. Literature-based model parameters were used to calculate NTCPs. Hypofractionated 3D-CRT (2.75 Gy/fraction, total dose 55 Gy) NTCPs of rectum, bladder and urethra were less than those for standard fractionated 4-field 3D-CRT (2-Gy/fraction, 64 Gy) and dose-escalated 4- and 5-field 3D-CRT (74 Gy). Rectal and bladder NTCPs (5.2% and 6.6%) following the dose-escalated 4-field 3D-CRT (74 Gy) were the highest among analyzed techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDRBT and 0.5% and 11.2% for HDR-BT. For Mammosite, NTCP was estimated to be 0.1 %, 0.1 %, 1.2% and 3.5% for skin desquamation, erythema, telangiectasia and fibrosis respectively (the source positioned at the balloon centre). A 4 mm Mammosite-balloon deformation leads to overdosing of PTV regions by ∼40%, resulting in excessive skin dose and increased NTCP. Conclusions Prostate brachytherapy resulted in NTCPs lower compared to external beam techniques. Mammosite-brachytherapy resulted in no heart/lung complications regardless of balloon deformation. However, 4 mm deformation caused 0.6% increase in tissue fibrosis NTCP.

Tissue doses in X-ray examinations of osteoarticular system

International Nuclear Information System (INIS)

Rabkin, I.Kh.; Stavitskij, R.V.; Blinov, N.N.; Vasil'ev, Yu.D.

1985-01-01

The X-ray method in diagnosis of the osteoarticular system disease is described. Problems on tissue dose distribution in X-ray examinations of a skeleton, a skull, humeral articulation, cervical, thoracic and lumbar vertebrae, hip joint, hipbones are considered. The values of specific tissue doses in roentgenography of the osteoarticular system are given

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

Energy Technology Data Exchange (ETDEWEB)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays.

Science.gov (United States)

Yi, Lan; Hu, Nan; Yin, Jie; Sun, Jing; Mu, Hongxiang; Dai, Keren; Ding, Dexin

2017-01-01

The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

The tissue injury and repair in cancer radiotherapy. A concept of tissue architecture and radio sensitivity

Energy Technology Data Exchange (ETDEWEB)

Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1975-06-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed.

Measurement of human normal tissue and tumour responses

International Nuclear Information System (INIS)

Ross, G.; Yarnold, J.R.

1988-01-01

The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

Extravascular transport in normal and tumor tissues.

Science.gov (United States)

Jain, R K; Gerlowski, L E

1986-01-01

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Modelling normal tissue isoeffect distribution in conformal radiotherapy of glioblastoma provides an alternative dose escalation pattern through hypofractionation without reducing the total dose

International Nuclear Information System (INIS)

Mangel, L.; Skriba, Z.; Major, T.; Polgar, C.; Fodor, J.; Somogyi, A.; Nemeth, G.

2002-01-01

The purpose of this study was to prove that by using conformal external beam radiotherapy (RT) normal brain structures can be protected even when applying an alternative approach of biological dose escalation: hypofractionation (HOF) without total dose reduction (TDR). Traditional 2-dimensional (2D) and conformal 3-dimensional (3D) treatment plans were prepared for 10 gliomas representing the subanatomical sites of the supratentorial brain. Isoeffect distributions were generated by the biologically effective dose (BED) formula to analyse the effect of conventionally fractionated (CF) and HOF schedules on both the spatial biological dose distribution and biological dose-volume histograms. A comparison was made between 2D-CF (2.0 Gy/day) and 3D-HOF (2.5 Gy/day) regimens, applying the same 60 Gy total doses. Integral biologically effective dose (IBED) and volumes received biologically equivalent to a dose of 54 Gy or more (V-BED54) were calculated for the lower and upper brain stem as organs of risk. The IBED values were lower with the 3D-HOF than with the 2D-CF schedule in each tumour location, means 22.7±17.1 and 40.4±16.9 in Gy, respectively (p<0.0001). The V-BED54 values were also smaller or equal in 90% of the cases favouring the 3D-HOF scheme. The means were 2.7±4.8 ccm for 3D-HOF and 10.7±12.7 ccm for 2D-CF (p=0.0006). Our results suggest that with conformal RT, fraction size can gradually be increased. HOF radiotherapy regimens without TDR shorten the treatment time and seem to be an alternative way of dose escalation in the treatment of glioblastoma

Modelling normal tissue isoeffect distribution in conformal radiotherapy of glioblastoma provides an alternative dose escalation pattern through hypofractionation without reducing the total dose

Energy Technology Data Exchange (ETDEWEB)

Mangel, L.; Skriba, Z.; Major, T.; Polgar, C.; Fodor, J.; Somogyi, A.; Nemeth, G. [National Research Inst. for Radiobiology and Radiohygiene, Budapest (Hungary)

2002-04-01

The purpose of this study was to prove that by using conformal external beam radiotherapy (RT) normal brain structures can be protected even when applying an alternative approach of biological dose escalation: hypofractionation (HOF) without total dose reduction (TDR). Traditional 2-dimensional (2D) and conformal 3-dimensional (3D) treatment plans were prepared for 10 gliomas representing the subanatomical sites of the supratentorial brain. Isoeffect distributions were generated by the biologically effective dose (BED) formula to analyse the effect of conventionally fractionated (CF) and HOF schedules on both the spatial biological dose distribution and biological dose-volume histograms. A comparison was made between 2D-CF (2.0 Gy/day) and 3D-HOF (2.5 Gy/day) regimens, applying the same 60 Gy total doses. Integral biologically effective dose (IBED) and volumes received biologically equivalent to a dose of 54 Gy or more (V-BED54) were calculated for the lower and upper brain stem as organs of risk. The IBED values were lower with the 3D-HOF than with the 2D-CF schedule in each tumour location, means 22.7{+-}17.1 and 40.4{+-}16.9 in Gy, respectively (p<0.0001). The V-BED54 values were also smaller or equal in 90% of the cases favouring the 3D-HOF scheme. The means were 2.7{+-}4.8 ccm for 3D-HOF and 10.7{+-}12.7 ccm for 2D-CF (p=0.0006). Our results suggest that with conformal RT, fraction size can gradually be increased. HOF radiotherapy regimens without TDR shorten the treatment time and seem to be an alternative way of dose escalation in the treatment of glioblastoma.

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

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Thorsten Schlomm

2013-03-01

Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

Differentiating cancerous from normal breast tissue by redox imaging

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2015-02-01

Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

Late change of normal tissue treated either by high dose rate or low dose rate interstitial brachytherapy. A retrospective comparative study on oral and oropharyngeal mucosa

International Nuclear Information System (INIS)

Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Inoue, Toshihiko

2002-01-01

The purpose of this study was to compare late changes of normal tissue treated either by high dose rate (HDR) or low dose rate (LDR) interstitial brachytherapy. For HDR group, 22 oropharynx cancer patients who were treated by HDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Osaka (Osaka Medical Center for Cancer and Cardiovascular Diseases and Osaka University Hospital) during June 1994 through April 2000 and came to the follow-up clinics during July 2000 through December 2000 were studied. For LDR group, 26 oropharynx cancer patients who were treated by LDR Ir-192 interstitial brachytherapy with/without external beam radiotherapy in Nancy (Centre Alexis Vautrin) during February 1989 through July 1998 and came to the follow-up clinics during April 1999 through July 1999 were studied. The standard HDR schedules were 54 Gy/9 fr/5-6 days for monotherapy and 18-24 Gy/3-4 fr/2-3 days following 45 Gy external beam radiotherapy. The standard LDR schedules were 65 Gy/5-6 days for monotherapy and 15-25 Gy/2-3 days following 50 Gy external beam radiotherapy. For evaluation of the late changes, we scored the mucosal and muscular changes inside the treated volume using the modified Dische score system and the RTOG/EORTC late radiation morbidity scoring scheme. For 6 items of the modified Dische score system, no significant difference was found between HDR and LDR groups. For the remaining 2 items (pallor, mobility impairment of faucial pillars), LDR group showed higher scores (p=0.010, 0.002). LDR group showed a trend toward higher scores for the RTOG/EORTC scheme (p=0.059). Some predict late effects by HDR interstitial brachytherapy to be severer than by LDR because no dose-rate effects can be expected. Our study, however, showed at least equivalent or even milder late changes by HDR. Appropriate fractionation schedule and extra geometrical sparing effects by optimized dose distribution of HDR group might result in milder late changes. With our

Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

International Nuclear Information System (INIS)

Tsubouchi, Susumu; Oohara, Hiroshi.

1989-01-01

Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

Absorbed dose calculation of the energy deposition close to bone, lung and soft tissue interfaces in molecular radiotherapy

International Nuclear Information System (INIS)

Fernandez, M.; Lassman, M.

2015-01-01

Full text of publication follows. Aim: for voxel-based dosimetry in molecular radiotherapy (MRT) based on tabulated voxel S-values these values are usually obtained only for soft tissue. In order to study the changes in the dose deposition patterns at interfaces between different materials we have performed Monte Carlo simulations. Methods: the deposited energy patterns were obtained using the Monte-Carlo radiation code MCNPX v2.7 for Lu 177 (medium-energy) and Y 90 (high-energy). The following interfaces were studied: soft tissue-bone and soft tissue-lungs. For this purpose a volume of soft tissue homogeneously filled with Lu 177 or Y 90 was simulated at the interface to 3 different volumes containing no activity: soft tissue, lungs and bone. The emission was considered to be isotropic. The dimensions were chosen to ensure that the energy deposited by all generated particles was scored. The materials were defined as recommended by ICPR46; the decay schemes of Eckerman and Endo were used. With these data the absorbed dose patterns normalized to the maximum absorbed dose in the source region (soft tissue) were calculated. Results: the absorbed dose fractions in the boundary with soft tissue, bone and lungs are 50%, 47% and 57%, respectively, for Lu 177 and 50%, 47% and 51% for Y 90 . The distances to the interface at which the absorbed fractions are at 0.1% are 1.0, 0.6 and 3.0 mm for Lu 177 and 7.0, 4.0 and 24 mm for Y 90 , for soft tissue, bone and lungs respectively. Conclusions: in MRT, the changes in the absorbed doses at interfaces between soft tissue and bone/lungs need to be considered for isotopes emitting high energy particles. (authors)

T lymphocytes and normal tissue responses to radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; McBride, William H.

2012-01-01

There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

HDR monotherapy for prostate cancer: A simulation study to determine the effect of catheter displacement on target coverage and normal tissue irradiation

International Nuclear Information System (INIS)

Kolkman-Deurloo, Inger-Karine K.; Roos, Martin A.; Aluwini, Shafak

2011-01-01

Purpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacement ensuring that both target coverage and normal tissue doses remain clinically acceptable. Besides the effect of total implant displacement, also displacements of catheters belonging to selected template rows only were evaluated in terms of target coverage and normal tissue dose, in order to analyse the change in dose distribution as a function of catheter dwell weight and catheter location. Material and methods: Five representative implant geometries, with 17 catheters each, were selected. The clinical treatment plan was compared to treatment plans in which an entire implant displacement in caudal direction over 3, 5, 7 and 10 mm was simulated. Besides, treatment plans were simulated considering a displacement of either the central, most ventral or most dorsal catheter rows only, over 5 mm caudally. Results: Due to displacement of the entire implant the target coverage drops below the tolerance of 93% for all displacements studied. The effect of displacement of the entire implant on organs at risk strongly depended on the patient anatomy; e.g., for 80% of the implant geometries the V 80 of the rectum exceeded its tolerance for all displacements. The effect of displacement of catheters belonging to selected template rows depended strongly on the relative weight of each catheter row when considering the target coverage and on its location when considering the dose in the organs at risk. Conclusion: This study supports the need for a check of the catheter locations before each fraction and correction of deviations of the catheter position exceeding 3 mm.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

Science.gov (United States)

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

Comparison of radiosensitivity between tumor and normal tissue in terms of cell population kinetics

International Nuclear Information System (INIS)

Sugahara, Tsutomu; Utsumi, Hiroshi

1975-01-01

Puck and Marcus in 1956 established the in vitro colony formation of mammalian cells and demonstrated a dose-survival curve of mammalian cells well fitted to the target theory. Since then almost all of the work on the radiosensitivity of malignant and normal cells has been based on the reproductive integrity of cells. However, in the author's laboratory, a recent work was done on the effect of ionizing radiation on the differentiative trait, using clonal cell cultures developed by Coon (1966) in chick embryonic cartilage cells. This work demonstrated clearly that the differentiative trait is more radiosensitive than is reproduction. Based on this finding a new compartment model is proposed for a cell renewal system which demonstrates the difference between normal and malignant tissue. (author)

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

Science.gov (United States)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

Energy Technology Data Exchange (ETDEWEB)

Cheryl G. Burrell, Ph.D.

2012-05-14

The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

Evaluating the Application of Tissue-Specific Dose Kernels Instead of Water Dose Kernels in Internal Dosimetry : A Monte Carlo Study

NARCIS (Netherlands)

Moghadam, Maryam Khazaee; Asl, Alireza Kamali; Geramifar, Parham; Zaidi, Habib

2016-01-01

Purpose: The aim of this work is to evaluate the application of tissue-specific dose kernels instead of water dose kernels to improve the accuracy of patient-specific dosimetry by taking tissue heterogeneities into consideration. Materials and Methods: Tissue-specific dose point kernels (DPKs) and

Analytical formulae in fractionated irradiation of normal tissue

International Nuclear Information System (INIS)

Kozubek, S.

1982-01-01

The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks.

Directory of Open Access Journals (Sweden)

Kai Rothkamm

Full Text Available Microbeam radiation therapy (MRT using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.

Comparative study of radiosensitivity of normal and regenerating tissues

International Nuclear Information System (INIS)

Samokhvalova, H.S.; Popova, M.F.

1983-01-01

A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer

International Nuclear Information System (INIS)

Chang, Joe Y.; Zhang Xiaodong; Wang Xiaochun; Kang Yixiu; Riley, Beverly C.; Bilton, Stephen C.; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.

2006-01-01

Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT

Effects of pions on normal tissues

International Nuclear Information System (INIS)

Tokita, N.

1981-01-01

Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

Simplified calculation method for radiation dose under normal condition of transport

International Nuclear Information System (INIS)

Watabe, N.; Ozaki, S.; Sato, K.; Sugahara, A.

1993-01-01

In order to estimate radiation dose during transportation of radioactive materials, the following computer codes are available: RADTRAN, INTERTRAN, J-TRAN. Because these codes consist of functions for estimating doses not only under normal conditions but also in the case of accidents, when nuclei may leak and spread into the environment by air diffusion, the user needs to have special knowledge and experience. In this presentation, we describe how, with a view to preparing a method by which a person in charge of transportation can calculate doses in normal conditions, the main parameters upon which the value of doses depends were extracted and the dose for a unit of transportation was estimated. (J.P.N.)

Tissue-phantom dose ratio R(t, F) in irradiation planning. 2

International Nuclear Information System (INIS)

Hegewald, H.

1986-01-01

The principles for measuring doses are represented to complete the developed tissue-phantom dose ratio R(t, F). The functional dependence of the tissue-phantom dose ratio on the field size results from the different spectral energy distribution in the buildup range compared to greater depths. This once more illustrates the demand, to move the calibration and reference depths into greater depths than the dose maximum depth on account of a high precision. The scattering factors and their dependence on the type of collimator are represented and tables are made up for practical use. In a supplement the derivations of the equation systems are given, to find out the tissue-phantom dose ratio by computation and the correspondence is tested. The measurements are more relevant in the megavolt range since dose values typically for the equipment are measured in the buildup range and depth dose tables are not available in the required completeness. (author)

Dose distribution around ion track in tissue equivalent material

International Nuclear Information System (INIS)

Zhang Wenzhong; Guo Yong; Luo Yisheng

2007-01-01

Objective: To study the energy deposition micro-specialty of ions in body-tissue or tissue equivalent material (TEM). Methods: The water vapor was determined as the tissue equivalent material, based on the analysis to the body-tissue, and Monte Carlo method was used to simulate the behavior of proton in the tissue equivalent material. Some features of the energy deposition micro-specialty of ion in tissue equivalent material were obtained through the analysis to the data from calculation. Results: The ion will give the energy by the way of excitation and ionization in material, then the secondary electrons will be generated in the progress of ionization, these electron will finished ions energy deposition progress. When ions deposited their energy, large amount energy will be in the core of tracks, and secondary electrons will devote its' energy around ion track, the ion dose distribution is then formed in TEM. Conclusions: To know biological effects of radiation , the research to dose distribution of ions is of importance(significance). (authors)

Pulse frequency in pulsed brachytherapy based on tissue repair kinetics

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Koedooder, Kees; Tienhoven, Geertjan van; Blank, Leo E.C.M.; Gonzalez Gonzalez, Dionisio

1998-01-01

Purpose: Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics. Method: Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an α/β ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h. Results: The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any α/β value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high α/β ratio and fast or intermediate repair half-time, and the RE for tissue with low α/β ratio and long repair half-time remains almost constant. Conclusion: Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics

Dose-rate effects in external beam radiotherapy redux

International Nuclear Information System (INIS)

Ling, C. Clifton; Gerweck, Leo E.; Zaider, Marco; Yorke, Ellen

2010-01-01

Recent developments in external beam radiotherapy, both in technical advances and in clinical approaches, have prompted renewed discussions on the potential influence of dose-rate on radio-response in certain treatment scenarios. We consider the multiple factors that influence the dose-rate effect, e.g. radical recombination, the kinetics of sublethal damage repair for tumors and normal tissues, the difference in α/β ratio for early and late reacting tissues, and perform a comprehensive literature review. Based on radiobiological considerations and the linear-quadratic (LQ) model we estimate the influence of overall treatment time on radio-response for specific clinical situations. As the influence of dose-rate applies to both the tumor and normal tissues, in oligo-fractionated treatment using large doses per fraction, the influence of delivery prolongation is likely important, with late reacting normal tissues being generally more sensitive to the dose-rate effect than tumors and early reacting tissues. In conventional fractionated treatment using 1.8-2 Gy per fraction and treatment times of 2-10 min, the influence of dose-rate is relatively small. Lastly, the dose-rate effect in external beam radiotherapy is governed by the overall beam-on-time, not by the average linac dose-rate, nor by the instantaneous dose-rate within individual linac pulses which could be as high as 3 x 10 6 MU/min.

Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

International Nuclear Information System (INIS)

Herschtal, Alan; Te Marvelde, Luc; Mengersen, Kerrie; Foroudi, Farshad; Eade, Thomas; Pham, Daniel; Caine, Hannah; Kron, Tomas

2015-01-01

Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes

Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

Energy Technology Data Exchange (ETDEWEB)

Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne (Australia); Te Marvelde, Luc [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Mengersen, Kerrie [School of Mathematical Sciences, Science and Engineering Faculty, Queensland University of Technology, Brisbane (Australia); Foroudi, Farshad [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Eade, Thomas [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Northern Clinical School, University of Sydney (Australia); Pham, Daniel [Department of Radiation Therapy, Peter MacCallum Cancer Centre, Melbourne (Australia); Caine, Hannah [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Kron, Tomas [The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne (Australia)

2015-06-01

Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.

β class II tubulin predominates in normal and tumor breast tissues

International Nuclear Information System (INIS)

Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

2003-01-01

Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

Evaluation of concave dose distributions created using an inverse planning system

International Nuclear Information System (INIS)

Hunt, Margie A.; Hsiung, C.-Y.; Spirou, Spirodon V.; Chui, C.-S.; Amols, Howard I.; Ling, Clifton C.

2002-01-01

Purpose: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. Methods and Materials: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV D max /PTV D 95 ) and maximum normal tissue doses (NT D max /PTV D 95 ). Results: In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5-8 mm) or strict NT dose constraints (10%-30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. Conclusion: Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest

Simulation studies of optimum energies for DXA: dependence on tissue type, patient size and dose model

International Nuclear Information System (INIS)

Michael, G. J.; Henderson, C. J.

1999-01-01

Dual-energy x-ray absorptiometry (DXA) is a well established technique for measuring bone mineral density (BMD). However, in recent years DXA is increasingly being used to measure body composition in terms of fat and fat-free mass. DXA scanners must also determine the soft tissue baseline value from soft-tissue-only regions adjacent to bone. The aim of this work is to determine, using computer simulations, the optimum x- ray energies for a number of dose models, different tissues, i.e. bone mineral, average soft tissue, lean soft tissue and fat; and a range of anatomical sites and patient sizes. Three models for patient dose were evaluated total beam energy, entrance exposure and absorbed dose calculated by Monte Carlo modelling. A range of tissue compositions and thicknesses were chosen to cover typical patient variations for the three sites femoral neck, PA spine and lateral spine. In this work, the optimisation of the energies is based on (1) the uncertainty that arises from the quantum statistical nature of the number of x-rays recorded by the detector, and (2) the radiation dose received by the patient. This study has deliberately not considered other parameters such as detector response, electronic noise, x-ray tube heat load etc, because these are technology dependent parameters, not ones that are inherent to the measuring technique. Optimisation of the energies is achieved by minimisation of the product of variance of density measurement and dose which is independent of the absolute intensities of the x-ray beams. The results obtained indicate that if solving for bone density, then E-low in the range 34 to 42 keV, E-high in the range 100 to 200 keV and incident intensity ratio (low energy/high energy) in the range 3 to 10 is a reasonable compromise for the normal range of patient sizes. The choice of energies is complicated by the fact that the DXA unit must also solve for fat and lean soft tissue in soft- tissue-only regions adjacent to the bone. In this

Tumor significant dose

International Nuclear Information System (INIS)

Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

1983-01-01

In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

Effect of tissue inhomogeneity on dose distribution of point sources of low-energy electrons

International Nuclear Information System (INIS)

Kwok, C.S.; Bialobzyski, P.J.; Yu, S.K.; Prestwich, W.V.

1990-01-01

Perturbation in dose distributions of point sources of low-energy electrons at planar interfaces of cortical bone (CB) and red marrow (RM) was investigated experimentally and by Monte Carlo codes EGS and the TIGER series. Ultrathin LiF thermoluminescent dosimeters were used to measure the dose distributions of point sources of 204 Tl and 147 Pm in RM. When the point sources were at 12 mg/cm 2 from a planar interface of CB and RM equivalent plastics, dose enhancement ratios in RM averaged over the region 0--12 mg/cm 2 from the interface were measured to be 1.08±0.03 (SE) and 1.03±0.03 (SE) for 204 Tl and 147 Pm, respectively. The Monte Carlo codes predicted 1.05±0.02 and 1.01±0.02 for the two nuclides, respectively. However, EGS gave consistently 3% higher dose in the dose scoring region than the TIGER series when point sources of monoenergetic electrons up to 0.75 MeV energy were considered in the homogeneous RM situation or in the CB and RM heterogeneous situation. By means of the TIGER series, it was demonstrated that aluminum, which is normally assumed to be equivalent to CB in radiation dosimetry, leads to an overestimation of backscattering of low-energy electrons in soft tissue at a CB--soft-tissue interface by as much as a factor of 2

Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

International Nuclear Information System (INIS)

Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

1981-01-01

Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration

Energy Technology Data Exchange (ETDEWEB)

Zhu, J; Liang, J; Chen, S; Qin, A; Yan, D [Beaumont Health Systeml, Royal Oak, MI (United States)

2016-06-15

Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition was used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

International Nuclear Information System (INIS)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

2015-01-01

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

Directory of Open Access Journals (Sweden)

Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

Comparison of effective atomic numbers of the cancerous and normal kidney tissue

International Nuclear Information System (INIS)

Manjunatha, H.C.

2015-01-01

The effective atomic number (Z eff ) and electron density (N e ) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Z eff and N e of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective N e with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Z eff in the dual-energy dividing radiography is also discussed. The values of Z eff and N e for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Z eff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

The tissue injury and repair in cancer radiotherapy

International Nuclear Information System (INIS)

Matsuzawa, Taiju

1975-01-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed. (author)

MO-DE-207A-09: Low-Dose CT Image Reconstruction Via Learning From Different Patient Normal-Dose Images

Energy Technology Data Exchange (ETDEWEB)

Han, H; Xing, L [Stanford University, Palo Alto, CA (United States); Liang, Z [Stony Brook University, Stony Brook, NY (United States)

2016-06-15

Purpose: To investigate a novel low-dose CT (LdCT) image reconstruction strategy for lung CT imaging in radiation therapy. Methods: The proposed approach consists of four steps: (1) use the traditional filtered back-projection (FBP) method to reconstruct the LdCT image; (2) calculate structure similarity (SSIM) index between the FBP-reconstructed LdCT image and a set of normal-dose CT (NdCT) images, and select the NdCT image with the highest SSIM as the learning source; (3) segment the NdCT source image into lung and outside tissue regions via simple thresholding, and adopt multiple linear regression to learn high-order Markov random field (MRF) pattern for each tissue region in the NdCT source image; (4) segment the FBP-reconstructed LdCT image into lung and outside regions as well, and apply the learnt MRF prior in each tissue region for statistical iterative reconstruction of the LdCT image following the penalized weighted least squares (PWLS) framework. Quantitative evaluation of the reconstructed images was based on the signal-to-noise ratio (SNR), local binary pattern (LBP) and histogram of oriented gradients (HOG) metrics. Results: It was observed that lung and outside tissue regions have different MRF patterns predicted from the NdCT. Visual inspection showed that our method obviously outperformed the traditional FBP method. Comparing with the region-smoothing PWLS method, our method has, in average, 13% increase in SNR, 15% decrease in LBP difference, and 12% decrease in HOG difference from reference standard for all regions of interest, which indicated the superior performance of the proposed method in terms of image resolution and texture preservation. Conclusion: We proposed a novel LdCT image reconstruction method by learning similar image characteristics from a set of NdCT images, and the to-be-learnt NdCT image does not need to be scans from the same subject. This approach is particularly important for enhancing image quality in radiation therapy.

MO-DE-207A-09: Low-Dose CT Image Reconstruction Via Learning From Different Patient Normal-Dose Images

International Nuclear Information System (INIS)

Han, H; Xing, L; Liang, Z

2016-01-01

Purpose: To investigate a novel low-dose CT (LdCT) image reconstruction strategy for lung CT imaging in radiation therapy. Methods: The proposed approach consists of four steps: (1) use the traditional filtered back-projection (FBP) method to reconstruct the LdCT image; (2) calculate structure similarity (SSIM) index between the FBP-reconstructed LdCT image and a set of normal-dose CT (NdCT) images, and select the NdCT image with the highest SSIM as the learning source; (3) segment the NdCT source image into lung and outside tissue regions via simple thresholding, and adopt multiple linear regression to learn high-order Markov random field (MRF) pattern for each tissue region in the NdCT source image; (4) segment the FBP-reconstructed LdCT image into lung and outside regions as well, and apply the learnt MRF prior in each tissue region for statistical iterative reconstruction of the LdCT image following the penalized weighted least squares (PWLS) framework. Quantitative evaluation of the reconstructed images was based on the signal-to-noise ratio (SNR), local binary pattern (LBP) and histogram of oriented gradients (HOG) metrics. Results: It was observed that lung and outside tissue regions have different MRF patterns predicted from the NdCT. Visual inspection showed that our method obviously outperformed the traditional FBP method. Comparing with the region-smoothing PWLS method, our method has, in average, 13% increase in SNR, 15% decrease in LBP difference, and 12% decrease in HOG difference from reference standard for all regions of interest, which indicated the superior performance of the proposed method in terms of image resolution and texture preservation. Conclusion: We proposed a novel LdCT image reconstruction method by learning similar image characteristics from a set of NdCT images, and the to-be-learnt NdCT image does not need to be scans from the same subject. This approach is particularly important for enhancing image quality in radiation therapy.

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

MRI characterization of brown adipose tissue in obese and normal-weight children

Energy Technology Data Exchange (ETDEWEB)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

2015-10-15

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

MRI characterization of brown adipose tissue in obese and normal-weight children

International Nuclear Information System (INIS)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

2015-01-01

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

International Nuclear Information System (INIS)

Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

1985-01-01

Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

1987-01-01

Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

Photon beam dose distributions for patients with implanted temporary tissue expanders

Science.gov (United States)

Asena, A.; Kairn, T.; Crowe, S. B.; Trapp, J. V.

2015-01-01

This study examines the effects of temporary tissue expanders (TTEs) on the dose distributions of photon beams in breast cancer radiotherapy treatments. EBT2 radiochromic film and ion chamber measurements were taken to quantify the attenuation and backscatter effects of the inhomogeneity. Results illustrate that the internal magnetic port present in a tissue expander causes a dose reduction of approximately 25% in photon tangent fields immediately downstream of the implant. It was also shown that the silicone elastomer shell of the tissue expander reduced the dose to the target volume by as much as 8%. This work demonstrates the importance for an accurately modelled high-density implant in the treatment planning system for post-mastectomy breast cancer patients.

THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

Science.gov (United States)

SNELL, E S; ATKINS, E

1965-06-01

Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

Science.gov (United States)

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

Science.gov (United States)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Probability distribution of dose rates in the body tissue as a function of the rhytm of Sr90 administration and the age of animals

International Nuclear Information System (INIS)

Rasin, I.M.; Sarapul'tsev, I.A.

1975-01-01

The probability distribution of tissue radiation doses in the skeleton were studied in experiments on swines and dogs. When introducing Sr-90 into the organism from the day of birth till 90 days dose rate probability distribution is characterized by one, or, for adult animals, by two independent aggregates. Each of these aggregates correspond to the normal distribution law

UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

Science.gov (United States)

Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

2015-10-10

A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

Statistical validation of normal tissue complication probability models

NARCIS (Netherlands)

Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

2012-01-01

PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

Science.gov (United States)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

International Nuclear Information System (INIS)

Zehentmayr, Franz; Söhn, Matthias; Exeli, Ann-Katrin; Wurstbauer, Karl; Tröller, Almut; Deutschmann, Heinz; Fastner, Gerd; Fussl, Christoph; Steininger, Philipp; Kranzinger, Manfred; Belka, Claus; Studnicka, Michael; Sedlmayer, Felix

2015-01-01

One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade ≥ 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: <2.5 cm 73.8 Gy, 2.5–4.5 cm 79.2 Gy, 4.5–6 cm 84.6 Gy, >6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP), two Lyman models and the cutoff-logistic regression model were fitted to the data with AE ≥ grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC c ), which calculates the model’s quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. The median follow up was 686 days (range 84–2921 days), 23/66 patients (35 %) experienced AE ≥ grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2–57.3) was the most significant predictor of AE ≥ grade 2 (HR = 1.05, CI 1.01–1.09, p = 0.007). Following high-dose accelerated radiotherapy the rate of AE ≥ grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the

Dose specification and normal tissue reference points in the treatment of cancer cervix

International Nuclear Information System (INIS)

Ray, D.K.; Kumar, P.; Misra, D.K.; Das, R.; Kumar, A.; Maji, T.; Chaudhuri, P.; Sinha, T.P.

2007-01-01

Carcinoma of uterine cervix is one of the most common diseases among the women in India where radiotherapy is the mainstay of treatment. Most common practice of dose prescription point is the Manchester Point A. American Brachytherapy Society (ABS) recommends a point H equivalent to that used in the classical Manchester system. Many centre practices Madison point M as dose specification point which is 20 mm cephaled along the tandem from a line joining the mid dwell positions in the ovoids/ring and 20 mm lateral to the tandem. In the present study has compared the dose prescription points between Manchester Point A and Madison Point M for ring applicators and their implication in the assessment of rectal and bladder doses in patients of Carcinoma of uterine cervix

Does low-dose CCK-8 injection produce abdominal pain in 'truly normal' individuals?

International Nuclear Information System (INIS)

Ramsay, S.; Webb, B.; Hille, N.

1999-01-01

Full text: The development of abdominal pain following cholecystokinin (CCK) injection is not specific for biliary disease. Patients can develop abdominal pain with CCK during hepatobiliary studies and have normal gallbladder function. Does this non-biliary pain indicate pathology? High doses of CCK induce pain in functional bowel syndromes, but may also produce pain in normals. Pain is less common at lower CCK doses, and hence may be more significant. This study aimed to determine the rate at which the low dose of CCK used in hepatobiliary scans causes abdominal pain and other side-effects in 'truly normal' individuals. Some preliminary results of CCK-induced pain in gastro-oesophageal reflux (GOR) patients are also discussed. Six 'truly normal' subjects were studied. 'Truly normal' was defined as: no current history of abdominal pain; no biliary or gallbladder disease; no significant GIT pathology; not currently on medication designed to be pharmacologically active in the GIT. Each patient was given an intravenous dose of 0.01 μg-kg -1 of CCK8 over 3 min, and side-effects were recorded for 30 min. No subject had abdominal pain. Two developed nausea, 1 moderate and 1 mild. An identical dose of CCK was given to 2 patients with endoscopically proven GOR. Anti-reflux medication had been ceased for 12 h. After CCK, 1 patient developed typical 'reflux' pain and 1 was asymptomatic. In conclusion, none of our 'truly normal' patients had abdominal pain with low-dose CCK. This suggests that patients developing pain following injection of this dose of CCK are indeed abnormal. The literature infers these patients may have irritable bowel syndrome; however, this hypothesis is complicated by our preliminary results indicating that CCK can reproduce pain in some patients with GOR

Reduction of dose enhancement from backscattered radiation at tissue-metal interfaces irradiated with 6MeV electrons

International Nuclear Information System (INIS)

Steel, B.

1996-01-01

Due to Electron Back Scatter (EBS), electron irradiation of tissue having under lying lead shielding results in an increase in dose to the tissue on the entrance side of the lead. In these situations dose increases as high as 80% have been reported in the literature. Saunders (British Journal of Radiology, 47, 467-470) noted that dose enhancement is dependent on atomic number of the under lying material approximately as Z 0.5 , and it increases at lower incident electron energies. In our clinic we use 2mm of lead shielding to protect under lying normal tissue when 6MeV electrons are used to treat lips and ears. The object of this study was to find the thinnest combination of materials to reduce the total dose to an acceptable level, with the provisos that; the patient does not come into contact with the lead or other metals, the finished shield could comfortabley be placed between the patient's lip and teeth, and that the materials are sufficietly malleable to work into custom shields. Various combinations of dental wax and aluminium were trialed. That which proved to give the best compromise between reduction of EBS and total shielding thickness was, 1mm of aluminim on the beam side of the lead with 1mm of dental wax to completely enclose the shield. In practice the manufactured shields are approximately 6 mm thick, and are usually not uncomfortable for the patient. (author)

MRI appearance of radiation-induced changes of normal cervical tissues

International Nuclear Information System (INIS)

Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

2001-01-01

Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation

International Nuclear Information System (INIS)

Matsushita, Satoru; Ando, Koichi; Koike, Sachiko

1994-01-01

To evaluate the protective effect of WR-151327 on late radiation-induced damaged to normal tissues in mice, the right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137 Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. Latae damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. WR-151327 has the potential to protect against radiation-induced late normal tissue damage. 17 refs., 6 figs., 2 tabs

Can cell survival parameters be deduced from non-clonogenic assays of radiation damage to normal tissue

International Nuclear Information System (INIS)

Michalowski, A.; Wheldon, T.E.; Kirk, J.

1984-01-01

The relationship between dose-response curves for large scale radiation injury to tissues and survival curves for clonogenic cells is not necessarily simple. Sterilization of clonogenic cells occurs near-instantaneously compared with the protracted lag period for gross injury to tissues. Moreover, with some types of macroscopic damage, the shapes of the dose-response curves may depend on time of assay. Changes in the area or volume of irradiated tissue may also influence the shapes of these curves. The temporal pattern of expression of large scale injury also varies between tissues, and two distinct groups can be recognized. In rapidly proliferating tissues, lag period is almost independent of dose, whilst in slowly proliferating tissues, it is inversely proportional to dose. This might be explained by invoking differences in corresponding proliferative structures of the tissues. (Three compartmental Type H versus one compartmental Type F proliferative organization). For the second group of tissues particularly, mathematical modelling suggests a systematic dissociation of the dose-response curves for clonogenic cell survival and large scale injury. In particular, it may be difficult to disentangle the contributions made to inter-fraction sparing by cellular repair processes and by proliferation-related factors. (U.K.)

Low dose X -ray effects on catalase activity in animal tissue

Science.gov (United States)

Focea, R.; Nadejde, C.; Creanga, D.; Luchian, T.

2012-12-01

This study was intended to investigate the effect of low-dose X ray-irradiation upon the activity of catalase (CAT) in freshly excised chicken tissues (liver, kidney, brain, muscle). The tissue samples were irradiated with 0.5Gy and 2Gy respectively, in a 6 MV photon beam produced by a clinical linear accelerator (VARIAN CLINAC 2100SC). The dose rate was of 260.88cGy/min. at 100 cm source to sample distance. The catalase level was assayed spectrophotometrically, based on reaction kinetics, using a catalase UV assay kit (SIGMA). Catalase increased activity in various tissue samples exposed to the studied X ray doses (for example with 24 % in the liver cells, pbonds that ensure the specificity of CAT active site) but the resulted balance of the two concurrent processes indicates the cell ability of decomposing the hydrogen peroxide-with benefits for the cell physiology restoration for the chosen low dose radiation.

Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

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A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

Changes in dose with segmentation of breast tissues in Monte Carlo calculations for low-energy brachytherapy

International Nuclear Information System (INIS)

Sutherland, J. G. H.; Thomson, R. M.; Rogers, D. W. O.

2011-01-01

Purpose: To investigate the use of various breast tissue segmentation models in Monte Carlo dose calculations for low-energy brachytherapy. Methods: The EGSnrc user-code BrachyDose is used to perform Monte Carlo simulations of a breast brachytherapy treatment using TheraSeed Pd-103 seeds with various breast tissue segmentation models. Models used include a phantom where voxels are randomly assigned to be gland or adipose (randomly segmented), a phantom where a single tissue of averaged gland and adipose is present (averaged tissue), and a realistically segmented phantom created from previously published numerical phantoms. Radiation transport in averaged tissue while scoring in gland along with other combinations is investigated. The inclusion of calcifications in the breast is also studied in averaged tissue and randomly segmented phantoms. Results: In randomly segmented and averaged tissue phantoms, the photon energy fluence is approximately the same; however, differences occur in the dose volume histograms (DVHs) as a result of scoring in the different tissues (gland and adipose versus averaged tissue), whose mass energy absorption coefficients differ by 30%. A realistically segmented phantom is shown to significantly change the photon energy fluence compared to that in averaged tissue or randomly segmented phantoms. Despite this, resulting DVHs for the entire treatment volume agree reasonably because fluence differences are compensated by dose scoring differences. DVHs for the dose to only the gland voxels in a realistically segmented phantom do not agree with those for dose to gland in an averaged tissue phantom. Calcifications affect photon energy fluence to such a degree that the differences in fluence are not compensated for (as they are in the no calcification case) by dose scoring in averaged tissue phantoms. Conclusions: For low-energy brachytherapy, if photon transport and dose scoring both occur in an averaged tissue, the resulting DVH for the entire

Changes in dose with segmentation of breast tissues in Monte Carlo calculations for low-energy brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Sutherland, J. G. H.; Thomson, R. M.; Rogers, D. W. O. [Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa K1S 5B6 (Canada)

2011-08-15

Purpose: To investigate the use of various breast tissue segmentation models in Monte Carlo dose calculations for low-energy brachytherapy. Methods: The EGSnrc user-code BrachyDose is used to perform Monte Carlo simulations of a breast brachytherapy treatment using TheraSeed Pd-103 seeds with various breast tissue segmentation models. Models used include a phantom where voxels are randomly assigned to be gland or adipose (randomly segmented), a phantom where a single tissue of averaged gland and adipose is present (averaged tissue), and a realistically segmented phantom created from previously published numerical phantoms. Radiation transport in averaged tissue while scoring in gland along with other combinations is investigated. The inclusion of calcifications in the breast is also studied in averaged tissue and randomly segmented phantoms. Results: In randomly segmented and averaged tissue phantoms, the photon energy fluence is approximately the same; however, differences occur in the dose volume histograms (DVHs) as a result of scoring in the different tissues (gland and adipose versus averaged tissue), whose mass energy absorption coefficients differ by 30%. A realistically segmented phantom is shown to significantly change the photon energy fluence compared to that in averaged tissue or randomly segmented phantoms. Despite this, resulting DVHs for the entire treatment volume agree reasonably because fluence differences are compensated by dose scoring differences. DVHs for the dose to only the gland voxels in a realistically segmented phantom do not agree with those for dose to gland in an averaged tissue phantom. Calcifications affect photon energy fluence to such a degree that the differences in fluence are not compensated for (as they are in the no calcification case) by dose scoring in averaged tissue phantoms. Conclusions: For low-energy brachytherapy, if photon transport and dose scoring both occur in an averaged tissue, the resulting DVH for the entire

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

Science.gov (United States)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

MISTRAL V1.1.1: assessing doses from atmospheric releases in normal and off-normal conditions

International Nuclear Information System (INIS)

David Kerouanton; Patrick Devin; Malvina Rennesson

2006-01-01

Protecting the environment and the public from radioactive and chemical hazards has always been a top priority for all companies operating in the nuclear domain. In this scope, SGN provides all the services the nuclear industry needs in environmental studies especially in relation to the impact assessment in normal operating conditions and risk assessment in off-normal conditions. In order to quantify dose impact on members of the public due to atmospheric releases, COGEMA and SGN developed MISTRAL V1.1.1 code. Dose impact depends strongly on dispersion of radionuclides in atmosphere. The main parameters involved in dispersion characterization are wind velocity and direction, rain, diffusion conditions, coordinates of the point of observation and stack elevation. MISTRAL code implements DOURY and PASQUILL Gaussian plume models which are widely used in the scientific community. These models, applicable for distances of transfer ranging from 100 m up to 30 km, are used to calculate atmospheric concentration and deposit at different distances from the point of release. MISTRAL allows the use of different dose regulations or dose coefficient databases such as: - ICRP30 and ICPR71 for internal doses (inhalation, ingestion) - Despres/Kocher database or US-EPA Federal Guidance no.12 (ICPR72 for noble gases) for external exposure (from plume or ground). The initial instant of the release can be considered as the origin of time or a date format can be specified (could be useful in a crisis context). While the context is specified, the user define the meteorological conditions of the release. In normal operating mode (routine releases), the user gives the annual meteorological scheme. The data can be recorded in the MISTRAL meteorological database. In off-normal conditions mode, MISTRAL V1.1 allows the use of successive release stages for which the user gives the duration, the meteorological conditions, that is to say stability class, wind speed and direction and rainfall

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

Present dose limits and their relation to radiosensitivity of different organs and tissues

International Nuclear Information System (INIS)

Anon.

1987-01-01

Dose equivalent limits in relation to dose thresholds are considered for injury of various tissues and organs to evaluate the protection agains non-stochastic irradiation effects by the existing system of dose limitation for radiotherapeutic personnel. Data on tissue radiosensitivity in relation to non-stochastic effects, obtained from radiotherapeutic experience, are presented. Dose threshold values, derived for patients, with a correction in the direction of increase, may be applied to conditions of occupational exposure except for bone marrow, gonads and eye lens, where threshold doses are lower

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

Science.gov (United States)

Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

International Nuclear Information System (INIS)

Majewski, Wojciech; Wesolowska, Iwona; Urbanczyk, Hubert; Hawrylewicz, Leszek; Schwierczok, Barbara; Miszczyk, Leszek

2009-01-01

Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanning during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to 70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm 3 for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm 3 for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder filling during RT could influence the dose distribution in the bladder and intestines. The dose distribution in the rectum and bowel was slightly better with

Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

Energy Technology Data Exchange (ETDEWEB)

Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

2011-12-01

Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

Badylak, S.F.; Babbs, C.F.

1984-01-01

The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

Acute and late effects of multimodal therapy on normal tissues

International Nuclear Information System (INIS)

Phillips, T.L.; Fu, K.K.

1977-01-01

The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

Science.gov (United States)

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to tissues and organs remain above IDRE thresholds).

Effect of low-density lateral interfaces on soft-tissue doses

International Nuclear Information System (INIS)

Hunt, Margie A.; Desobry, Gregory E.; Fowble, Barbara; Coia, Lawrence R.

1997-01-01

Purpose: Doses at the interface between tissue and low-density inhomogeneities with the interface positioned perpendicular to the beam direction have been well studied. When the inhomogeneity lies parallel to the beam direction (i.e., a lateral interface), the resulting dose distribution is not as well known. Lateral lung--soft-tissue interfaces are common in many fields used to treat malignancies in the thorax region including tangential breast fields and anteroposterior fields for lung and esophageal cancer. The purpose of this study was to evaluate the dose distribution along lateral interfaces and to determine the implications for treatment. Methods and Materials: A polystyrene and cork slab phantom was irradiated from the side to simulate treatment fields with lateral lung--soft-tissue interfaces. The beam was positioned with the isocenter in polystyrene and the field edge in cork. Cork slabs (0.6-2.5 cm) were used to simulate different thicknesses of lung between the field edge and the target volume. Measurements were made using a parallel plate ionization chamber. With the chamber position held constant, polystyrene slabs were added between the cork and the chamber to study the dose distribution in the interface region. Interface doses were studied as a function of the amount of cork in the field, field size, beam energy (6-18 MV), and depth. Results: Doses in the interface region were lower by as much as 10% compared to doses in a homogeneous phantom. For a given cork width and field size, the magnitude of the underdose increased by several percent as the x-ray energy increased from 6 to 18 MV. The underdose at the interface was 5% for 6 MV and 8% for 18 MV X-rays with a 1-cm cork width. For a 2.5-cm cork width, underdoses of 2.5% and 3% at distances up to 2.5 and 4 mm lateral to the interface were observed for 6- and 18-MV X-rays, respectively. However, doses right at the interface were 1% greater for 6 MV and 3% less for 18 MV than doses in a homogeneous

Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

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Therése Andersson

Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

International Nuclear Information System (INIS)

Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

2009-01-01

Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

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Flickinger, J C; Kalend, A [Pittsburgh University School of Medicine (USA). Department of Radiation Oncology Pittsburg Cancer Institute (USA)

1990-03-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab.

Use of normalized total dose to represent the biological effect of fractionated radiotherapy

International Nuclear Information System (INIS)

Flickinger, J.C.; Kalend, A.

1990-01-01

There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab

SU-E-T-154: Calculation of Tissue Dose Point Kernels Using GATE Monte Carlo Simulation Toolkit to Compare with Water Dose Point Kernel

Energy Technology Data Exchange (ETDEWEB)

Khazaee, M [shahid beheshti university, Tehran, Tehran (Iran, Islamic Republic of); Asl, A Kamali [Shahid Beheshti University, Tehran, Iran., Tehran, Tehran (Iran, Islamic Republic of); Geramifar, P [Shariati Hospital, Tehran, Iran., Tehran, Tehran (Iran, Islamic Republic of)

2015-06-15

Purpose: the objective of this study was to assess utilizing water dose point kernel (DPK)instead of tissue dose point kernels in convolution algorithms.to the best of our knowledge, in providing 3D distribution of absorbed dose from a 3D distribution of the activity, the human body is considered equivalent to water. as a Result tissue variations are not considered in patient specific dosimetry. Methods: In this study Gate v7.0 was used to calculate tissue dose point kernel. the beta emitter radionuclides which have taken into consideration in this simulation include Y-90, Lu-177 and P-32 which are commonly used in nuclear medicine. the comparison has been performed for dose point kernels of adipose, bone, breast, heart, intestine, kidney, liver, lung and spleen versus water dose point kernel. Results: In order to validate the simulation the Result of 90Y DPK in water were compared with published results of Papadimitroulas et al (Med. Phys., 2012). The results represented that the mean differences between water DPK and other soft tissues DPKs range between 0.6 % and 1.96% for 90Y, except for lung and bone, where the observed discrepancies are 6.3% and 12.19% respectively. The range of DPK difference for 32P is between 1.74% for breast and 18.85% for bone. For 177Lu, the highest difference belongs to bone which is equal to 16.91%. For other soft tissues the least discrepancy is observed in kidney with 1.68%. Conclusion: In all tissues except for lung and bone, the results of GATE for dose point kernel were comparable to water dose point kernel which demonstrates the appropriateness of applying water dose point kernel instead of soft tissues in the field of nuclear medicine.

SU-E-T-154: Calculation of Tissue Dose Point Kernels Using GATE Monte Carlo Simulation Toolkit to Compare with Water Dose Point Kernel

International Nuclear Information System (INIS)

Khazaee, M; Asl, A Kamali; Geramifar, P

2015-01-01

Purpose: the objective of this study was to assess utilizing water dose point kernel (DPK)instead of tissue dose point kernels in convolution algorithms.to the best of our knowledge, in providing 3D distribution of absorbed dose from a 3D distribution of the activity, the human body is considered equivalent to water. as a Result tissue variations are not considered in patient specific dosimetry. Methods: In this study Gate v7.0 was used to calculate tissue dose point kernel. the beta emitter radionuclides which have taken into consideration in this simulation include Y-90, Lu-177 and P-32 which are commonly used in nuclear medicine. the comparison has been performed for dose point kernels of adipose, bone, breast, heart, intestine, kidney, liver, lung and spleen versus water dose point kernel. Results: In order to validate the simulation the Result of 90Y DPK in water were compared with published results of Papadimitroulas et al (Med. Phys., 2012). The results represented that the mean differences between water DPK and other soft tissues DPKs range between 0.6 % and 1.96% for 90Y, except for lung and bone, where the observed discrepancies are 6.3% and 12.19% respectively. The range of DPK difference for 32P is between 1.74% for breast and 18.85% for bone. For 177Lu, the highest difference belongs to bone which is equal to 16.91%. For other soft tissues the least discrepancy is observed in kidney with 1.68%. Conclusion: In all tissues except for lung and bone, the results of GATE for dose point kernel were comparable to water dose point kernel which demonstrates the appropriateness of applying water dose point kernel instead of soft tissues in the field of nuclear medicine

Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

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Ben-Zhou Feng

2016-04-01

Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Barber, J.B.P.; Burrill, W.; Spreadborough, A.R.; Levine, E.; Warren, C.; Scott, D.; Kiltie, A.E.; Roberts, S.A.

2000-01-01

There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. Radiosensitivity was assessed using a macronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G 0 phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predisposition? Br. J. Cancer 1998;77;614-620) and an assay of G 2 phase chromatid radiosensitivity ('G 2 assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G 2 assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the 'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G 2 assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998

Determination of the tissue inhomogeneity correction in high dose rate Brachytherapy for Iridium-192 source

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Barlanka Ravikumar

2012-01-01

Full Text Available In Brachytherapy treatment planning, the effects of tissue heterogeneities are commonly neglected due to lack of accurate, general and fast three-dimensional (3D dose-computational algorithms. In performing dose calculations, it is assumed that the tumor and surrounding tissues constitute a uniform, homogeneous medium equivalent to water. In the recent past, three-dimensional computed tomography (3D-CT based treatment planning for Brachytherapy applications has been popularly adopted. However, most of the current commercially available planning systems do not provide the heterogeneity corrections for Brachytherapy dosimetry. In the present study, we have measured and quantified the impact of inhomogeneity caused by different tissues with a 0.015 cc ion chamber. Measurements were carried out in wax phantom which was employed to measure the heterogeneity. Iridium-192 (192 Ir source from high dose rate (HDR Brachytherapy machine was used as the radiation source. The reduction of dose due to tissue inhomogeneity was measured as the ratio of dose measured with different types of inhomogeneity (bone, spleen, liver, muscle and lung to dose measured with homogeneous medium for different distances. It was observed that different tissues attenuate differently, with bone tissue showing maximum attenuation value and lung tissue resulting minimum value and rest of the tissues giving values lying in between those of bone and lung. It was also found that inhomogeneity at short distance is considerably more than that at larger distances.

Dose-rate effects between 0.3 and 30 Gy/h in a normal and a malignant human cell line

International Nuclear Information System (INIS)

Amdur, R.J.; Bedford, J.S.

1994-01-01

This study used continuous open-quotes intermediateclose quotes dose rate irradiation (0.3-30 Gy/h) to compare the capacity for and repair of sublethal radiation damage in different cell lines growing in tissue culture. Two human cell lines were studied; one was derived from normal human fibroblasts (AG1522) and the other from a squamous cell carcinoma of the uterine cervix (HTB-35). Dose-response curves for clonogenic survival were determined following irradiation of plateau-phase cultures at five different dose rates: 22.6, 6.12, 3.65, 1.04, and 0.38 Gy/h. Subculture following irradiation was delayed for 8-24 h to allow for the full repair of open-quotes potentially lethal damage.close quotes A significant dose-rate effect was seen in both cell lines. For irradiation at the highest dose rate, survival at 2 Gy (SF2) and the α/β ratio were similar for the two cell lines (approximately 0.7 and 8.0 Gy, respectively) but the half-time of repair of sublethal damage was estimated to be approximately five times longer in the normal human fibroblast line (154 min) than in the carcinoma (31 min) cell line. These results indicate that measuring the dose-rate effect between 0.3 and 30 Gy/h is a useful way to identify and quantify differences in sublethal damage repair between cell lines. To the extent that in vitro and in vivo repair parameters are similar, and that representative tumor biopsy specimens can be examined in this way, this approach may provide a prospective way of determining the dose rate (brachytherapy) or fractionation schedule that will optimize the therapeutic ratio. 32 refs., 1 fig

Low dose X –ray effects on catalase activity in animal tissue

International Nuclear Information System (INIS)

Focea, R; Nadejde, C; Creanga, D; Luchian, T

2012-01-01

This study was intended to investigate the effect of low-dose X ray-irradiation upon the activity of catalase (CAT) in freshly excised chicken tissues (liver, kidney, brain, muscle). The tissue samples were irradiated with 0.5Gy and 2Gy respectively, in a 6 MV photon beam produced by a clinical linear accelerator (VARIAN CLINAC 2100SC). The dose rate was of 260.88cGy/min. at 100 cm source to sample distance. The catalase level was assayed spectrophotometrically, based on reaction kinetics, using a catalase UV assay kit (SIGMA). Catalase increased activity in various tissue samples exposed to the studied X ray doses (for example with 24 % in the liver cells, p<0.05) suggested the stimulation of the antioxidant enzyme biosynthesis within several hours after exposure at doses of 0.5 Gy and 2 Gy; the putative enzyme inactivation could also occur (due to the injuries on the hydrogen bonds that ensure the specificity of CAT active site) but the resulted balance of the two concurrent processes indicates the cell ability of decomposing the hydrogen peroxide-with benefits for the cell physiology restoration for the chosen low dose radiation.

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Characterization of the dose perturbation in tissue by stents as a function of external beam energy

International Nuclear Information System (INIS)

Schell, M.C.; Rosenzweig, D.P.; Weaver, K.A.; Rubin, P.

1997-01-01

Purpose: External beam irradiation of coronary arteries was shown to be detrimental in an animal model for the prevention of neointimal hyperplasia in the presence of stents when orthovoltage x-ray beams are used. This present study investigated the effect of beam energy on the dose distribution in the wall of the artery as a function of energy in the presence of stents in order to ascertain the effect on the dose due to beam energy. Materials and Methods: 250 kVp x-rays and 6-MV x rays were used to irradiate a stent placed in an homogeneous phantom. Radiochromic film densitometry and Monte Carlo calculations were used to measure and to simulate the dose distribution in the proximity of the stent. Result: External beam irradiation was reported to not only fail to prevent neointimal hyperplasia, but actually accentuate the neointimal response to a prompt mechanical injury in the artery. The photoelectric effect, which dominates low-energy x-ray interactions, produces recoil electrons in the stent which enhance the dose surrounding intima. The photoelectrons generated in nickel and iron have an extremely short range in normal tissue, approximately 0.1 mm. Initial estimates of orthovoltage x-ray interactions with the stent indicate a dose enhancement in the orthovoltage range by a factor of 2 to 3 due to the rise in the photoelectric cross section in this energy range depending on the elemental composition of the stent. Film densitometry verifies this dose enhancement. The Monte Carlo calculations yield a dose enhancement and the dose fall off with distance from the stent when irradiated with orthovoltage x-rays. Conversely when the tissue and stent are irradiated with megavoltage x-rays, the dose enhancement in this region is a factor of 1.15 in close proximity to the stent and 1.0 at distances greater than 0.1 mm. 6-MV photon interactions in tissue and iron are predominantly through Compton scattering. The Compton effect is dependent on the electron density in the

Radiobiological predictors of tumor and acute normal tissue response in radiotherapy for head and neck cancers

International Nuclear Information System (INIS)

Maciejewski, B.; Skladowski, K.; Zajusz, A.

1991-01-01

The importance of measurements of the potential doubling time (T pot. ) and of the survival fraction at 2.0 Gy (SF 2 ), and a method modifying acute radiation response of normal oral mucosa are discussed. Tumor clonogen repopulation accelerates around day 28 of the treatment, and the rate of repopulation is not constant but continuously increases from about 0.3 Gy/day to 1.0-1.3 Gy/day between day 28 and 65 of the treatment. This may suggest that T pot. values decrease correspondingly. The relevance of prior-to-treatment T pot. measurements to clinical situations is discussed. The SF 2 value reflects the intrinsic radiosensitivity of human tumors. The SF 2 values are expected to be valuable as predictors for tumor response to irradiation. Variations in the SF 2 values depending on tumor characteristics and assay methods are discussed in relation to the dose response and tumor cure probability. The effect of modifying the repopulation rate in the oral mucosa by stimulation with a 2% silver nitrate solution is discussed. Although these prognosticators are different in their nature, they might provide a rational basis for selecting patients into optimal irradiation treatment and might allow to modify the radiation response of dose-limiting normal tissues. (author). 5 figs., 1 tab., 28 refs

Relative effect of dose-rate values and fractionation on late responding tissues and tumours

International Nuclear Information System (INIS)

Malgieri, F.

1995-01-01

There are currently available different facilities for radiotherapy also with regard to the dose-rate values (in the ranges LDR - MDR - HDR), sometimes used alternatively or subsequently for the same tumour. We have set up a 'unitary' L-Q model, based on Liversage's and Dale's works, that explicitly include also the dose-rate value and a correction factor of the β parameter depending on the sublethal damage repair time constant, on the length of time of each irradiation and on the time interval between following irradiation for to realize the effect of the incomplete repair when the time interval is short as, for example, in the PLDR. This 'unitary' L-Q model is, of course, usable in the same way both for external beam therapy and for curietherapy and make possible to compute and compare, for each kind of tumour and normal tissue, the relative effect of the different available modality of radiotherapy also with regard to the dose-rate. We show and discuss the resulting relationships of the ratio BED 'late'/BED tumour changing the time-dose parameters and the values of the biological characteristic parameters T p , α/β and μ, for defined size of tumour control and different value of the doserate

Converting dose distributions into tumour control probability

International Nuclear Information System (INIS)

Nahum, A.E.

1996-01-01

The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s a can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s a . The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs

Converting dose distributions into tumour control probability

Energy Technology Data Exchange (ETDEWEB)

Nahum, A E [The Royal Marsden Hospital, London (United Kingdom). Joint Dept. of Physics

1996-08-01

The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s{sub a} can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s{sub a}. The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs.

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

International Nuclear Information System (INIS)

Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G.A.V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P.V.B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-01-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

DEFF Research Database (Denmark)

Horsman, Michael R

2017-01-01

INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

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Jun Zhang

2015-01-01

Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.

Modification of transmission dose algorithm for irregularly shaped radiation field and tissue deficit

Energy Technology Data Exchange (ETDEWEB)

Yun, Hyong Geon; Shin, Kyo Chul [Dankook Univ., College of Medicine, Seoul (Korea, Republic of); Huh, Soon Nyung; Woo, Hong Gyun; Ha, Sung Whan [Seoul National Univ., College of Medicine, Seoul (Korea, Republic of); Lee, Hyoung Koo [The Catholic Univ., College of Medicine, Seoul (Korea, Republic of)

2002-07-01

Algorithm for estimation of transmission dose was modified for use in partially blocked radiation fields and in cases with tissue deficit. The beam data was measured with flat solid phantom in various conditions of beam block. And an algorithm for correction of transmission dose in cases of partially blocked radiation field was developed from the measured data. The algorithm was tested in some clinical settings with irregular shaped field. Also, another algorithm for correction of transmission dose for tissue deficit was developed by physical reasoning. This algorithm was tested in experimental settings with irregular contours mimicking breast cancer patients by using multiple sheets of solid phantoms. The algorithm for correction of beam block could accurately reflect the effect of beam block, with error within {+-}1.0%, both with square fields and irregularly shaped fields. The correction algorithm for tissue deficit could accurately reflect the effect of tissue deficit with errors within {+-}1.0% in most situations and within {+-}3.0% in experimental settings with irregular contours mimicking breast cancer treatment set-up. Developed algorithms could accurately estimate the transmission dose in most radiation treatment settings including irregularly shaped field and irregularly shaped body contour with tissue deficit in transmission dosimetry.

Modification of transmission dose algorithm for irregularly shaped radiation field and tissue deficit

International Nuclear Information System (INIS)

Yun, Hyong Geon; Shin, Kyo Chul; Huh, Soon Nyung; Woo, Hong Gyun; Ha, Sung Whan; Lee, Hyoung Koo

2002-01-01

Algorithm for estimation of transmission dose was modified for use in partially blocked radiation fields and in cases with tissue deficit. The beam data was measured with flat solid phantom in various conditions of beam block. And an algorithm for correction of transmission dose in cases of partially blocked radiation field was developed from the measured data. The algorithm was tested in some clinical settings with irregular shaped field. Also, another algorithm for correction of transmission dose for tissue deficit was developed by physical reasoning. This algorithm was tested in experimental settings with irregular contours mimicking breast cancer patients by using multiple sheets of solid phantoms. The algorithm for correction of beam block could accurately reflect the effect of beam block, with error within ±1.0%, both with square fields and irregularly shaped fields. The correction algorithm for tissue deficit could accurately reflect the effect of tissue deficit with errors within ±1.0% in most situations and within ±3.0% in experimental settings with irregular contours mimicking breast cancer treatment set-up. Developed algorithms could accurately estimate the transmission dose in most radiation treatment settings including irregularly shaped field and irregularly shaped body contour with tissue deficit in transmission dosimetry

Dose effect comparisons between HFR and BMRR irradiated dogs with respect to healthy tissue tolerance

International Nuclear Information System (INIS)

Huiskamp, R.; Philipp, K.H.I.; Gavin, P.R.; Wheeler, F.J.; Siefert, A.

1993-01-01

Epithermal neutron beams are being developed for the application of boron neutron capture therapy (BNCT) of deep seated tumors, like glioblastoma and astrocytomas, through the intact skin. Epithermal neutrons will be moderated by the tissue mass between skin and tumour to produce the thermal neutrons necessary for the 10 B(n,α) 7 Li reaction in the target tissue. Although the neutron capture cross-sections of elements in normal tissue are several orders of magnitude lower that for boron, the high abundance of hydrogen and nitrogen will cause a significant contribution to the total absorbed radiation dose through the 1 H(n,γ) 2 H and the 14 N(n,p) 14 C reaction, respectively. Due to inevitable incomplete filtration, an epithermal beam will also contain a fast neutron component, i.e. neutrons with energies ≥ 10 keV, and a γ-photon component originating from the reactor and produced in structural and filter materials. Therefore, the resultant radiation consists of a complex of low and high LET radiation of which the constitutents vary rapidly with depth in tissue. Based on the ongoing canine healthy tissue tolerance study at the Brookhaven Medical Research Reactor (BMRR) using the epithermal beam without BSH, the relative biological effectiveness (RBE) of the fast neutron beam component has been determined for skin reactions. In addition, a open-quotes compound factorclose quotes, i.e geometry x RBE, for the 10 B(n,α) 7 Li reaction was derived for dogs irradiated at the BMRR with the epithermal beam and BSH (Gavin et al.). Currently, a healthy tissue tolerance study with BSH is being carried out at the HB11 epithermal beam of the High Flux Reactor at Petten. The present paper describes preliminary dose effect comparisons between High Flux Reactor (HFR) and BMRR irradiated dogs with respect to healthy tissue tolerance in order to refine the BSH compound factors and the fast neutron RBE for skin and brain

Determination of electron depth-dose curves for water, ICRU tissue, and PMMA and their application to radiation protection dosimetry

International Nuclear Information System (INIS)

Grosswendt, B.

1994-01-01

For monoenergetic electrons in the energy range between 60 keV and 10 MeV, normally incident on water, 4-element ICRU tissue and PMMA phantoms, depth-dose curves have been calculated using the Monte Carlo method. The phantoms' shape was that of a rectangular solid with a square front face of 30 cm x 30 cm and a thickness of 15 cm; it corresponds to that recommended by the ICRU for use in the procedure of calibrating radiation protection dosemeters. The depth-dose curves have been used to determine practical ranges, half-value depths, electron fluence to maximum absorbed dose conversion factors, and conversion factors between electron fluence and absorbed dose at depths d corresponding to 0.007 g.cm -2 , 0.3 g.cm -2 , and 1.0 g.cm -2 . The latter data can be used as fluence to dose equivalent conversion factors for extended parallel electron beams. (Author)

Applicability of the tissue stem cell turnover concept on the validity of cumulative dose based radiation risk evaluation

International Nuclear Information System (INIS)

Otsuka, Kensuke; Hamada, Nobuyuki; Iwasaki, Toshiyasu; Yoshida, Kazuo

2011-01-01

The radiation protection system adopts the linear no-threshold model to achieve proper radiation protection for considering cancer risks resulting from radiation exposure. This model uses cumulative dose to a tissue for risk evaluation in which cumulative dose is related to the amount of DNA damage and consequential induction of gene mutation. In this concept, gene mutation accumulates in tissue stem cells, the putative target of carcinogenesis, with total dose given to the tissue. Unlike high-dose-rate exposure, epidemiological studies in high radiation background areas, such as Kerala in India, revealed that cancer risks is not elevated by the dose to the inhabitants, suggesting that there exists some mechanisms to eliminate the damage/mutation in the exposed tissue under extremely low-dose-rate exposure situations. In this report, the dynamics of tissue stem cell turnover is evaluated as a possible mechanism under extremely low-dose-rate exposure situations. To this end, we reviewed recent literatures studying tissue stem cell turnover, and found that great advances in stem cell research have made it possible to trace a fate of stem cells in tissues. Furthermore, turnover of tissue stem cells is found to occur after irradiation, due to competition of stem cells within tissues. This raises a possibility that radiation effects may not accumulate in a tissue depending on the dose-rate and duration of exposure period. (author)

MCNP Code in Assessment of Variations of Effective Dose with Torso Adipose Tissue Thickness

International Nuclear Information System (INIS)

Massoud, E.

2005-01-01

The effective dose is the unite used in the field of radiation protection. It is a well defined doubly weighted uantity involving both physical and biological variables. Several factors may induce variation in the effective dose in different individuals of similar exposure data. One of these factors is the variation of adipose tissue thickness in different exposed individuals. This study essentially concenrs the assessment of the possible variation in the effective dose due to variation in the thickness of adipose tissue. The study was done using MCNP4b code to perform mathematical model of the human body depending on that given to the reference man developed by International Commission of Radiological Protection (ICRP), and calculate the effective dose with different thicknessess of adipose tissues. The study includes a comprehensive appraisal of the Monte Cario simulation, the Medical Internal Radiation Dose (MIRD) model for the human body, and the various mathematical considerations involved in the radiation dose calculations for the various pertinent parts of the human body. The radiation energies considered were 80 KeV, 300 KeV and I MeV, applying two exposure positions; anteroposterior (AP), postero-anterior (PA) with different adipose tissue thickness. This study is a theoretical approach based on detailed mathematical calculations of great precision that deals with all considerations involved in the mechanisms of radiation energy absorption in biological system depending on the variation in the densities of the particular in biological system depending on the variation in the densities of the particular tissues. The results obtained indicate that maximum decrease in effective dose occures with the lowest energy at 5cm adipose tissues thickeness for both AP and PA exposure positions. The results obtained were compared to similar work previsouly done using MCNP4 b showing very good agreement

Application of biological dose concept in dose optimization for conformal radiotherapy of prostate carcinoma

International Nuclear Information System (INIS)

Li Yunhai; Liao Yuan; Zhou Lijun; Pan Ziqiang; Feng Yan

2003-01-01

Objective: On basis of physical dose optimization, LQ model was used to investigate the difference between the curves of biological effective dose and physical isodose. The influence of applying the biological dose concept on three dimensional conformal radiotherapy of prostate carcinoma was discussed. Methods: Four treatment plannings were designed for physical dose optimization: three fields, four-box fields, five fields and six fields. Target dose uniformity and protection of the critical tissue-rectum were used as the principal standard for designing the treatment planning. Biological effective dose (BED) was calculated by LQ model. The difference between the BED curve drawn in the central layer and the physical isodose curve was studied. The difference between the adjusted physical dose (APD) and the physical dose was also studied. Results: Five field planning was the best in target dose uniformity and protection of the critical tissue-rectum. The physical dose was uniform in the target, but the biological effective doses revealed great discrepancy in the biological model. Adjusted physical dose distribution also displayed larger discrepancy than the physical dose unadjusted. Conclusions: Intensified Modulated Radiotherapy (IMRT) technique with inversion planning using biological dose concept may be much more advantageous to reach a high tumor control probability and low normal tissue complication probability

The difference of scoring dose to water or tissues in Monte Carlo dose calculations for low energy brachytherapy photon sources.

Science.gov (United States)

Landry, Guillaume; Reniers, Brigitte; Pignol, Jean-Philippe; Beaulieu, Luc; Verhaegen, Frank

2011-03-01

The goal of this work is to compare D(m,m) (radiation transported in medium; dose scored in medium) and D(w,m) (radiation transported in medium; dose scored in water) obtained from Monte Carlo (MC) simulations for a subset of human tissues of interest in low energy photon brachytherapy. Using low dose rate seeds and an electronic brachytherapy source (EBS), the authors quantify the large cavity theory conversion factors required. The authors also assess whether ap plying large cavity theory utilizing the sources' initial photon spectra and average photon energy induces errors related to spatial spectral variations. First, ideal spherical geometries were investigated, followed by clinical brachytherapy LDR seed implants for breast and prostate cancer patients. Two types of dose calculations are performed with the GEANT4 MC code. (1) For several human tissues, dose profiles are obtained in spherical geometries centered on four types of low energy brachytherapy sources: 125I, 103Pd, and 131Cs seeds, as well as an EBS operating at 50 kV. Ratios of D(w,m) over D(m,m) are evaluated in the 0-6 cm range. In addition to mean tissue composition, compositions corresponding to one standard deviation from the mean are also studied. (2) Four clinical breast (using 103Pd) and prostate (using 125I) brachytherapy seed implants are considered. MC dose calculations are performed based on postimplant CT scans using prostate and breast tissue compositions. PTV D90 values are compared for D(w,m) and D(m,m). (1) Differences (D(w,m)/D(m,m)-1) of -3% to 70% are observed for the investigated tissues. For a given tissue, D(w,m)/D(m,m) is similar for all sources within 4% and does not vary more than 2% with distance due to very moderate spectral shifts. Variations of tissue composition about the assumed mean composition influence the conversion factors up to 38%. (2) The ratio of D90(w,m) over D90(m,m) for clinical implants matches D(w,m)/D(m,m) at 1 cm from the single point sources, Given

Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

International Nuclear Information System (INIS)

Slatter, J.G.; Sams, J.P.; Easter, J.A.

2003-01-01

Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [ 14 C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [ 14 C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [ 14 C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled 14 CO 2 . After 7 daily [ 14 C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C max and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

Energy Technology Data Exchange (ETDEWEB)

Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

2003-05-01

Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

Changes in the rate of proliferation in normal tissues after irradiation

International Nuclear Information System (INIS)

Denekamp, J.

1975-01-01

In tissues where reproductive cell death is known to cause the functional tissue damage (e.g., intestine and skin), repopulation becomes important only after the death of the radiation-damaged cells. Since these tissues have a fairly rapid turnover, this can occur within a short period of time and can assist in the healing of tissues during fractionated therapy. However, in tissues which express their damage late, such as the lung, it is very unlikely that repopulation will be stimulated before cell death is manifested and this does not occur during the period over which fractionated radiotherapy is administered. Although repopulation may be of no importance in these tissues, e.g., lungs and kidneys, there appears to be some other ''repair'' process which requires additional radiation dose to be administered to achieve the same endpoint if the overall time is increased

Alpha-particle doses to human organs and tissues from internally-deposited 226Ra and 228Ra

International Nuclear Information System (INIS)

Keane, A.T.; Schlenker, R.A.

1981-01-01

Estimation of radiation doses to the soft tissues from internally-deposited 226 Ra and 228 Ra is relevant to an investigation of soft-tissue malignancies in radium-exposed persons being conducted at the Center for Human Radiobiology. Alpha-particle doses in a 50-year period following a single injection of 226 Ra or 228 Ra are presented for 31 soft tissues and organs of the adult human. The dose estimates were derived from the ICRP alkaline earth model fitted to data on retention of 226 Ra in soft tissues and bone, combined with reported ratios of 226 Ra to Ca in soft tissue and bone at natural levels and the distribution of Ca in the tissues of Reference Man (ICRP23). The median of the 31 organ and tissue doses from the α-particles of 226 Ra itself is 0.08 rad per injected μCi. An additional average dose of 0.01 rad per μCi 226 Ra daughter products produced in soft tissue or transferred from bone to soft tissue. Soft-tissue doses from α-particles of the 228 Ra decay series are about six times those from 226 Ra α-particles for equal injected activities of 228 Ra and 226 Ra, with the assumption that 228 Ra daughter products do not transfer from the organ in which they are produced. The 50-year dose to the red marrow of bone from α-particles originating in bone is 0.55 rad per μCi 226 Ra injected and 1.0 rad per μCi 228 Ra injected. For ingestion by dial painters of luminous compound containg 226 Ra or 228 Ra with a daughter-to-parent activity ratio of 0.5, the dose to the mucosal alyer of the lower large intestine from α-particles originating in the gut contents is about 0.1 rad per μCi systemic intake of 226 Ra or 228 Ra

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

Energy Technology Data Exchange (ETDEWEB)

Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

2010-07-15

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Qualitative dose response of the normal canine head to epithermal neutron irradiation with and without boron capture

International Nuclear Information System (INIS)

DeHaan, C.E.; Gavin, P.R.; Kraft, S.L.; Wheeler, F.J.; Atkinson, C.A.

1992-01-01

Boron Neutron Capture Therapy is being re-evaluated for the treatment of intracranial tumors. Prior to human clinical trials, determination of normal tissue tolerance is critical. Dogs were chosen as a large animal model for the following reasons. Dogs can be evaluated with advanced imaging, diagnostic and therapeutic modalities. Dogs are amenable to detailed neurologic examination and subtle behavioral changes are easily detected. Specifically, Labrador retrievers were chosen for their large body and head size. The dogs received varying doses of epithermal neutron irradiation and boron neutron capture irradiation using an epithermal neutron source. The dogs were closely monitored for up to one year post irradiation

A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

Energy Technology Data Exchange (ETDEWEB)

Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

2012-08-01

Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

International Nuclear Information System (INIS)

Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

2012-01-01

Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

Assessment of radiation doses due to normal operation, incidents and accidents of the final disposal facility

International Nuclear Information System (INIS)

Rossi, J.; Raiko, H.; Suolanen, V.; Ilvonen, M.

1999-03-01

Radiation doses for workers of the encapsulation and disposal facility and for inhabitants in the environment caused by the facility during its operation were considered. The study covers both the normal operation of the plant and some hypothetical incidents and accidents. Occupational radiation doses inside the plant during normal operation are based on the design basis, assuming that highest permitted dose levels are prevailing in control rooms during fuel transfer and encapsulation processes. Release through the ventilation stack is assumed to be filtered both in normal operation and in hypothetical incident and accident cases. Calculation of the offsite doses from normal operation is based on the hypothesis that one fuel pin per 100 fuel bundles for all batches of spent fuel transported to the encapsulation facility is leaking. The release magnitude in incidents and accidents is based on the event chains, which lead to loss of fuel pin tightness followed by a discharge of radionuclides into the handling chamber and to some degree through the ventilation stack into atmosphere. The weather data measured at the Olkiluoto meteorological mast was employed for calculating of offsite doses. Therefore doses could be calculated in a large amount of different dispersion conditions, the statistical frequencies of which have, been measured. Finally doses were combined into cumulative distributions, from which a dose value representing the 99.5 % confidence level, is presented. The dose values represent the exposure of a critical group, which is assumed to live at the distance of 200 meters from the encapsulation and disposal plant and thus it will receive the largest doses in most dispersion conditions. Exposure pathways considered were: cloudsnine, inhalation, groundshine and nutrition (milk of cow, meat of cow, green vegetables, grain and root vegetables). Nordic seasonal variation is included in ingestion dose models. The results obtained indicate that offsite doses

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

Energy Technology Data Exchange (ETDEWEB)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

2011-05-18

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

International Nuclear Information System (INIS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Lind, Bengt K.; Brahme, Anders

2011-01-01

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ 2 -distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint

A new tissue segmentation method to calculate 3D dose in small animal radiation therapy.

Science.gov (United States)

Noblet, C; Delpon, G; Supiot, S; Potiron, V; Paris, F; Chiavassa, S

2018-02-26

In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Z eff ) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Z eff ) in small animal dose calculation. The method is based on the relationship found between CBCT number and ρ*Z eff product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZ eff variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZ eff method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations. The study of the impact of ρZ eff variation over the range of materials, from ρZ eff  = 2 g.cm - 3 (lung) to 27 g.cm - 3 (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZ eff method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose

Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

Energy Technology Data Exchange (ETDEWEB)

Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

2012-07-15

In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

Nominal effective radiation doses delivered during clinical trials of boron neutron capture therapy

International Nuclear Information System (INIS)

Capala, J.; Diaz, A.Z.; Chanana, A.D.

1997-01-01

Boron neutron capture therapy (BNCT) is a binary system that, in theory, should selectively deliver lethal, high linear energy transfer (LET) radiation to tumor cells dispersed within normal tissues. It is based on the nuclear reaction 10-B(n, α)7-Li, which occurs when the stable nucleus of boron-10 captures a thermal neutron. Due to the relatively high cross-section of the 10-B nucleus for thermal neutron capture and short ranges of the products of this reaction, tumor cells in the volume exposed to thermal neutrons and containing sufficiently high concentration of 10-B would receive a much higher radiation dose than the normal cells contained within the exposed volume. Nevertheless, radiation dose deposited in normal tissue by gamma and fast neutron contamination of the neutron beam, as well as neutron capture in nitrogen, 14-N(n,p)14-C, hydrogen, 1-H(n,γ)2-H, and in boron present in blood and normal cells, limits the dose that can be delivered to tumor cells. It is, therefore, imperative for the success of the BNCT the dosed delivered to normal tissues be accurately determined in order to optimize the irradiation geometry and to limit the volume of normal tissue exposed to thermal neutrons. These are the major objectives of BNCT treatment planning

Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

International Nuclear Information System (INIS)

Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

2006-01-01

Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

The influence of dose per fraction on repair kinetics

International Nuclear Information System (INIS)

Rojas, A.; Joiner, M.C.

1989-01-01

The use of multiple fractions per day (MFD) in radiotherapy requires information about the rate of repair of radiation injury. It is important to know the minimum interval between fractions necessary for maximum sparing of normal tissue damage, whether rate of repair is dependent on the size of dose per fraction and if it is different in early and late responding tissues and in tumours. To address these questions, the rate of repair between radiation dose fractions was measured in mouse skin (acute damage), mouse kidney (late damage) and a mouse tumour (carcinoma NT). Skin and kidney measurements were made using multiple split doses of X-rays, followed by a neutron top-up. For skin, faster recovery was obtained with 4.4 Gy fractions (t1/2 = 3.46 ± 0.88 h). In contrast kidney showed slower recovery at a low dose per fraction of 2 Gy (t1/2 = 1.69 ± 0.39 h) than at a higher dose of 7 Gy per fraction (t1/2 = 0.92 ± 0.1h). These data show that repair rate is dependent on the size of dose per fraction, but not in a simple way. T1/2 values now available for many different tissues generally lie in the range of 1-2h, and are not correlated with proliferation status or early versus late response to treatment. At the doses used currently in clinical MFD treatments, these data indicate that damage in almost all normal tissues would increase if interfraction intervals less than 6 h were used. The t1/2 for CaNT (0.31 ± 0.15 h) is less than for any normal tissue. This underlines that the excess morbidity resulting from interfraction intervals < 6 h will not be paralleled by an increased effect in tumours. (author). 25 refs.; 7 figs

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

Science.gov (United States)

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Dose prescription in boron neutron capture therapy

International Nuclear Information System (INIS)

Gupta, N.M.S.; Gahbauer, R.A.; Blue, T.E.; Wambersie, A.

1994-01-01

The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the 10 B microdistribution in normal tissue, and the ratio of 10 B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and 10 B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D max shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs

A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

2010-01-01

Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitam...

Dose modification factors in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Allen, B.J. (Australian Nuclear Science and Technology Organization (ANSTO), Menai (Australia))

1993-01-01

The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. (orig.).

Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

Energy Technology Data Exchange (ETDEWEB)

Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail: sorl@rn.dk; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)

2013-10-15

Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

International Nuclear Information System (INIS)

Zhao, Q L; Guo, Z Y; Wei, H J; Guo, X; Zhong, H Q; Li, L Q; Si, J L; Yang, H Q; Xie, S S; Wu, G Y; Li, X Y

2011-01-01

We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10 -5 cm/s in normal esophagus and (2.45±0.06)×10 -5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G

Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

Science.gov (United States)

Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

2011-01-01

We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

International Nuclear Information System (INIS)

Plevova, P.

2002-01-01

Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

Measurement of californium-252 gamma photons depth dose distribution in tissue equivalent material. Vol. 4

Energy Technology Data Exchange (ETDEWEB)

Fadel, M A; El-Fiki, M A; Eissa, H M; Abdel-Hafez, A; Naguib, S H [National Institute of Standards, Cairo (Egypt)

1996-03-01

Phantom of tissue equivalent material with and without bone was used measuring depth dose distribution of gamma-rays from californium-252 source. The source was positioned at center of perspex walled phantom. Depth dose measurements were recorded for X, Y and Z planes at different distances from source. TLD 700 was used for measuring the dose distribution. Results indicate that implantation of bone in tissue equivalent medium cause changes in the gamma depth dose distribution which varies according to variation in bone geometry. 9 figs.

Estimate of the absorbed dose in the mouse organs and tissues after tritium administration

International Nuclear Information System (INIS)

Saito, Masahiro

2000-01-01

Chronic and accidental release of tritium from future fusion facilities may cause some extent of hazardous effect to the public health. Various experiments using small animals such as mice have been performed to mimic the dose accumulation due to tritium intake by the human body. An difficulty in such animal experiments using small animals is that it is rather difficult to administer tritium orally and estimate the dose to small organs or tissues. In the course of our study, a simple method to administer THO and T-labeled amino acids orally to the mouse was dictated and dose accumulation in various organs and tissues was determined. The tritium retention in the bone marrow was also determined using the micro-centrifuge method. Throughout our experiment, colony-bred DDY mice were used. The 8-10 week old male mice were orally and intraperitoneally administered THO water or T-amino acids mixture solution. For the purpose of oral administration, a 10 μl aliquot of T-containing saline solution was placed on the tongue of the mice using an automatic micropipette. At various times after tritium administration, the animals were sacrificed and the amount of tritium in various tissues and organs including bone marrow was examined. Dose accumulation pattern after THO intake and T-amino acids was compared between intraperitoneal injection and oral administration. The accumulated dose after oral administration of THO exhibited a tendency to be 10-20% higher than after intraperitoneal injection. The bone marrow dose after oral intake of THO was found to be lower than the doses to urine, blood, liver and testis. In contrast, the blood dose gave a conservative estimate for the dose to the other tissues and organs. (author)

Dose constraints in paediatric radiotherapy; Contraintes de dose en radiotherapie pediatrique

Energy Technology Data Exchange (ETDEWEB)

Bernier, V. [Groupe de radiotherapie pediatrique SFCE, Centre Alexis-Vautrin, 54 - Nancy (France)

2010-10-15

The author discusses the issue of dose constraints for organs at risk when performing paediatric radiotherapy, and outlines that this issue is only partially resolved by the QUANTEC publication (quantitative estimates of normal tissue effects in the clinic). Then, he presents a guide elaborated by the French group of paediatric radiotherapists. This guide reviews organs at risk, imagery delineation requirements, dose constraints and short-, medium- and long-term consequences of organ irradiation. Short communication

Low-Dose Hyper-Radiosensitivity Is Not a Common Effect in Normal Asynchronous and G2-Phase Fibroblasts of Cancer Patients

International Nuclear Information System (INIS)

Słonina, Dorota; Biesaga, Beata; Janecka, Anna; Kabat, Damian; Bukowska-Strakova, Karolina; Gasińska, Anna

2014-01-01

Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells were irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis

TU-D-209-06: Head and Neck Tissue Dose From X-Ray Scatter to Physicians Performing Cardiovascular Procedures

Energy Technology Data Exchange (ETDEWEB)

Fetterly, K; Schueler, B; Grams, M [Mayo Clinic, Rochester, MN (United States); Sturchio, G [Mayo Clinic, Jacksonville, FL (United States)

2016-06-15

Purpose: The purpose of this work was to characterize the spatial distribution of scatter radiation to the head and neck of a physician performing an x-ray interventional procedure and assess brain, eye lens, and carotid artery dose. Methods: Radiographic x-ray beams were tuned to match the peak energy (56 to 106 keV) and HVL (3.5 to 6.5 mm Al) of x-ray scatter originating from a patient during a fluoroscopic procedure. The radiographic beam was directed upon a Rando phantom from an inferior-left location to mimic a typical patient-operator geometric relationship. A lead-equivalent protective garment was secured to the phantom. Direct exposure Gafchromic film (XRQA2) was placed between the transverse plane layers of the head and neck region of the phantom and exposed with 4 scatter-equivalent radiographic beams. A 3×3 cm{sup 2} film placed at the left collar of the phantom was used to monitor incident dose in the position of a radiation monitoring badge. The films were converted to 2D dose distribution maps using FilmQA Pro software and an Epson 11000-XL scanner. The 2D dose distributions maps were normalized by the left collar dose and the percent of left collar dose (%LCD) was calculated for select tissues. Results: The dose maps had high dynamic range (10{sub 4}) and spatial detail. Considering all transverse planes and 4 scatter beam qualities, the median %LCD values were: whole brain 8.5%, left brain 13%, right brain 5.4%, left eye lens 67%, right eye lens 25%, left carotid artery 72%, and right carotid artery 28%. Conclusion: Scatter radiation dose to an operator can be simulated using a tuned radiographic beam and used to expose a phantom and Gafchromic film, thereby creating detailed 2D dose distribution maps. This work facilitates individualized estimation of dose to select head and neck tissues based on an operator’s radiation monitoring badge value.

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

International Nuclear Information System (INIS)

Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

1988-01-01

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

Correlation study of trace metals in malignant and normal breast tissues by AAS technique

International Nuclear Information System (INIS)

Rahman, S.

2012-01-01

The study reports the application of atomic absorption spectrophotometry (AAS) for quantification of Fe, Cu and Zn in forty one formalin-fixed biopsy breast carcinoma tissue and adjoining fifteen normal tissue samples. These tissues samples were of category two breast carcinoma patients and of normal subjects. The qualitative comparison between the elements levels measured in the two types of specimens suggests significant elevation of these metals in the histopathological samples of carcinoma tissue. The samples were collected from women aged 19-51 years. Most of the patients belong to urban areas of Pakistan and middle to high socioeconomic status with the exception of few. Findings of study depicts that these elements have an important role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu and Zn was observed. The results showed the excessive accumulation of Fe (166.9 mg/L) in tissue samples of breast carcinoma patients (p < 0.01) than that in normal tissues samples (23.5 mg/L). In order to validate our method of analysis certified reference material Muscle Tissue Lyophilised (IAEA) MA-M-2/TM was analyzed for Fe, Cu and Zn. Determined concentrations were in good agreement with certified levels. The concentration distribution of trace elements Cu, Zn and Fe measured in the malignant tissues were found to be higher when compared to benign tissues, indicating the involvement of these metals in the breast malignancy. Results also indicate that excess iron may play a role in breast carcinogenesis. (Orig./A.B.)

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Liu, J; Eldib, A; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Lin, M [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States); Li, J [Cyber Medical Inc, Xian, Shaanxi (China); Mora, G [Universidade de Lisboa, Codex, Lisboa (Portugal)

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number was used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.

Genetic markers for prediction of normal tissue toxicity after radiotherapy

DEFF Research Database (Denmark)

Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

2008-01-01

During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

International Nuclear Information System (INIS)

Wheldon, T.E.; Michalowski, A.S.

1982-01-01

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

Low-dose caffeine discrimination and self-reported mood effects in normal volunteers.

Science.gov (United States)

Silverman, K; Griffiths, R R

1992-01-01

A caffeine versus placebo discrimination procedure was used to determine the lowest caffeine dose that could produce discrimination and self-reported mood effects in normal volunteers. During daily sessions under double-blind conditions, caffeine-abstinent subjects orally ingested a capsule containing 178 mg caffeine or placebo. Before beginning discrimination training, the compounds were identified to subjects by letter codes. Fifteen, 30, and 45 min after capsule ingestion, subjects guessed the capsule's letter code. Correct guesses at 45 min earned money. After each session, subjects received a supplementary capsule containing caffeine or placebo to ensure that, within each phase of the study, subjects received the same daily dose of caffeine equal to the training dose. Five of the 15 subjects acquired the caffeine versus placebo discrimination within the first 20 sessions (greater than or equal to 75% correct); 6 other subjects acquired the discrimination with additional training. Nine subjects who acquired the discrimination were subsequently trained at progressively lower caffeine doses. In general, the lowest dose to produce discrimination (greater than or equal to 75% correct) was also the lowest dose to produce self-reported mood effects: 4 subjects showed discrimination and self-reported mood effects at 100 mg caffeine, 2 at 56 mg, 1 at 32 mg, and 1 at 18 mg. One of these subjects also showed self-reported mood effects at 10 mg. The present study documents discriminative stimulus and self-reported mood effects of caffeine at doses below those previously shown to affect any behavior in normal volunteers. PMID:1548451

Effects of low dose irradiation on NK activity of normal individuals and patients with cancer

International Nuclear Information System (INIS)

Tian Hailin; Su Liaoyuan

1994-10-01

Effects of low dose irradiation on NK activity of lymphocytes and on K 562 cells were studied. The NK activity was determined by means of 3 H-TdR release assay. While 3 H-TdR incorporation was used to reflect functional changes of K 562 cells after low dose irradiation. 21 patients with cancer and 10 normal individuals were detected. The results indicated that the NK activity of lymphocytes in normal individuals increased significantly after 10 and 50 cGy γ-ray irradiation, while in patients with cancer the NK activity of lymphocytes increased only at the dose of 50 cGy irradiation. The increase of NK activity in normal individuals was higher than that in patients with cancer after same doses of irradiation. When K 562 cells were irradiated by 10 cGy γ-rays, the 3 H-TdR incorporation value increased. After exposed to over 50 cGy the stimulating effect disappeared

MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

International Nuclear Information System (INIS)

Wu, Q; Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N

2015-01-01

Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API

MO-F-CAMPUS-T-01: Radiosurgery of Multiple Brain Metastases with Single-Isocenter VMAT: Optimizing Treatment Geometry to Reduce Normal Brain Dose

Energy Technology Data Exchange (ETDEWEB)

Wu, Q [Wayne State University, Detroit, MI (United States); Snyder, K; Liu, C; Huang, Y; Li, H; Chetty, I; Wen, N [Henry Ford Health System, Detroit, MI (United States)

2015-06-15

Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas were the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.

Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

International Nuclear Information System (INIS)

Wilson, W.R.; Patterson, A.V.

2003-01-01

There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

Evaluation of subject contrast and normalized average glandular dose by semi-analytical models

International Nuclear Information System (INIS)

Tomal, A.; Poletti, M.E.; Caldas, L.V.E.

2010-01-01

In this work, two semi-analytical models are described to evaluate the subject contrast of nodules and the normalized average glandular dose in mammography. Both models were used to study the influence of some parameters, such as breast characteristics (thickness and composition) and incident spectra (kVp and target-filter combination) on the subject contrast of a nodule and on the normalized average glandular dose. From the subject contrast results, detection limits of nodules were also determined. Our results are in good agreement with those reported by other authors, who had used Monte Carlo simulation, showing the robustness of our semi-analytical method.

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

Science.gov (United States)

Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A model for dose estimation in therapy of liver with intraarterial microspheres

International Nuclear Information System (INIS)

Zavgorodni, S.F.

1996-01-01

Therapy with intraarterial microspheres is a technique which involves incorporation of radioisotope-labelled microspheres into a capillary bed of tumour and normal tissue. Beta-emitters such as 90 Y and 166 Ho are used for this purpose. This technique provides tumour to normal tissue (TNT) dose ratios in the range of 2-10 and demonstrates significant clinical benefit, which could potentially be increased with more accurate dose predictions and delivery. However, dose calculations in this modality face the difficulties associated with nonuniform and inhomogeneous activity distribution. Most of the dose calculations used clinically do not account for the nonuniformity and assume uniform activity distribution. This paper is devoted to the development of a model which would allow more accurate prediction of dose distributions from microspheres. The model calculates dose assuming that microspheres are aggregated into randomly distributed clusters, and using precomputed dose kernels for the clusters. The dose kernel due to a microsphere cluster was found by numerical integration of a point source dose kernel over the volume of the cluster. It is shown that a random distribution of clusters produces an intercluster distance distribution which agrees well with the one measured by Pillai et al in liver. Dose volume histograms (DVHs) predicted by the model agree closely with the results of Roberson et al for normal tissue and tumour. Dose distributions for different concentrations and types of radioisotope, as well as for tumours of different radii, have been calculated to demonstrate the model's possible applications. (author)

Liver perfusion CT during hepatic arteriography for the hepatocellular carcinoma: Dose reduction and quantitative evaluation for normal- and ultralow-dose protocol

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Shingo [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan); Katada, Yoshiaki, E-mail: yoshiaki@dokkyomed.ac.jp [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan); Gohkyu, Masaki; Nakajima, Masahiro; Kawabata, Hideyuki; Nozaki, Miwako [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan)

2012-12-15

Objectives: The purpose of this study was to investigate whether substantial reduction of the computed tomography (CT) dose is possible in liver CT perfusion imaging by comparing the results of ultralow-dose CT perfusion imaging with those of conventional CT perfusion imaging the same patients and under the same conditions. Materials and methods: The study was composed following two parts: computer simulation and patients study. In computer simulation, noise was added to the images so that the standard deviation (SD) of the CT values in the liver parenchyma became various values using ImageJ. Time density curves (TDCs) were created from the simulated data, and the influence of difference in the SDs on the shapes of the TDCs was investigated. In the patient study, CT perfusion during intra-arterial injection was performed in 30 consecutive patients undergoing transcatheter arterial chemoembolization. CT perfusion images were acquired twice, at 100 mA (CTDI{sub vol}, 300 mGy) for normal and at 20 mA (CTDI{sub vol}, 60 mGy) for the ultralow radiation doses, under the same conditions. Results: No change was observed in the shape of the TDCs and peak values in the analysis of simulation images. A very good correlation was observed between the normal- and ultralow-dose CT images for all analyzed values (R{sup 2} = 0.9885 for blood flow, 0.9269 for blood volume, and 0.8424 for mean transit time). Conclusions: Our results demonstrated that there was no significant difference in the analysis results of perfusion CT between ultralow-dose CT performed using 20% of the conventional dose and normal-dose CT perfusion.

Assessments for high dose radionuclide therapy treatment planning

International Nuclear Information System (INIS)

Fisher, D.R.

2003-01-01

Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

NARCIS (Netherlands)

Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

Is the assumption of normality or log-normality for continuous response data critical for benchmark dose estimation?

International Nuclear Information System (INIS)

Shao, Kan; Gift, Jeffrey S.; Setzer, R. Woodrow

2013-01-01

Continuous responses (e.g. body weight) are widely used in risk assessment for determining the benchmark dose (BMD) which is used to derive a U.S. EPA reference dose. One critical question that is not often addressed in dose–response assessments is whether to model the continuous data as normally or log-normally distributed. Additionally, if lognormality is assumed, and only summarized response data (i.e., mean ± standard deviation) are available as is usual in the peer-reviewed literature, the BMD can only be approximated. In this study, using the “hybrid” method and relative deviation approach, we first evaluate six representative continuous dose–response datasets reporting individual animal responses to investigate the impact on BMD/BMDL estimates of (1) the distribution assumption and (2) the use of summarized versus individual animal data when a log-normal distribution is assumed. We also conduct simulation studies evaluating model fits to various known distributions to investigate whether the distribution assumption has influence on BMD/BMDL estimates. Our results indicate that BMDs estimated using the hybrid method are more sensitive to the distribution assumption than counterpart BMDs estimated using the relative deviation approach. The choice of distribution assumption has limited impact on the BMD/BMDL estimates when the within dose-group variance is small, while the lognormality assumption is a better choice for relative deviation method when data are more skewed because of its appropriateness in describing the relationship between mean and standard deviation. Additionally, the results suggest that the use of summarized data versus individual response data to characterize log-normal distributions has minimal impact on BMD estimates. - Highlights: • We investigate to what extent the distribution assumption can affect BMD estimates. • Both real data analysis and simulation study are conducted. • BMDs estimated using hybrid method are more

Is the assumption of normality or log-normality for continuous response data critical for benchmark dose estimation?

Energy Technology Data Exchange (ETDEWEB)

Shao, Kan, E-mail: Shao.Kan@epa.gov [ORISE Postdoctoral Fellow, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gift, Jeffrey S. [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Setzer, R. Woodrow [National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

2013-11-01

Continuous responses (e.g. body weight) are widely used in risk assessment for determining the benchmark dose (BMD) which is used to derive a U.S. EPA reference dose. One critical question that is not often addressed in dose–response assessments is whether to model the continuous data as normally or log-normally distributed. Additionally, if lognormality is assumed, and only summarized response data (i.e., mean ± standard deviation) are available as is usual in the peer-reviewed literature, the BMD can only be approximated. In this study, using the “hybrid” method and relative deviation approach, we first evaluate six representative continuous dose–response datasets reporting individual animal responses to investigate the impact on BMD/BMDL estimates of (1) the distribution assumption and (2) the use of summarized versus individual animal data when a log-normal distribution is assumed. We also conduct simulation studies evaluating model fits to various known distributions to investigate whether the distribution assumption has influence on BMD/BMDL estimates. Our results indicate that BMDs estimated using the hybrid method are more sensitive to the distribution assumption than counterpart BMDs estimated using the relative deviation approach. The choice of distribution assumption has limited impact on the BMD/BMDL estimates when the within dose-group variance is small, while the lognormality assumption is a better choice for relative deviation method when data are more skewed because of its appropriateness in describing the relationship between mean and standard deviation. Additionally, the results suggest that the use of summarized data versus individual response data to characterize log-normal distributions has minimal impact on BMD estimates. - Highlights: • We investigate to what extent the distribution assumption can affect BMD estimates. • Both real data analysis and simulation study are conducted. • BMDs estimated using hybrid method are more

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

Science.gov (United States)

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

Science.gov (United States)

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

Determination of dose equivalent with tissue-equivalent proportional counters

International Nuclear Information System (INIS)

Dietze, G.; Schuhmacher, H.; Menzel, H.G.

1989-01-01

Low pressure tissue-equivalent proportional counters (TEPC) are instruments based on the cavity chamber principle and provide spectral information on the energy loss of single charged particles crossing the cavity. Hence such detectors measure absorbed dose or kerma and are able to provide estimates on radiation quality. During recent years TEPC based instruments have been developed for radiation protection applications in photon and neutron fields. This was mainly based on the expectation that the energy dependence of their dose equivalent response is smaller than that of other instruments in use. Recently, such instruments have been investigated by intercomparison measurements in various neutron and photon fields. Although their principles of measurements are more closely related to the definition of dose equivalent quantities than those of other existing dosemeters, there are distinct differences and limitations with respect to the irradiation geometry and the determination of the quality factor. The application of such instruments for measuring ambient dose equivalent is discussed. (author)

Dose distribution following selective internal radiation therapy

International Nuclear Information System (INIS)

Fox, R.A.; Klemp, P.F.; Egan, G.; Mina, L.L.; Burton, M.A.; Gray, B.N.

1991-01-01

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y

Gustatory tissue injury in man: radiation dose response relationships and mechanisms of taste loss

International Nuclear Information System (INIS)

Mossman, K.L.

1986-01-01

In this report dose response data for gustatory tissue damage in patients given total radiation doses ranging from 3000 to 6000 cGy are presented. In order to evaluate direct radiation injury to gustatory tissues as a mechanism of taste loss, measurements of damage to specific taste structures in bovine and murine systems following radiation exposure in the clinical range are correlated to taste impairment observed in radiotherapy patients. (author)

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

International Nuclear Information System (INIS)

Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

2010-01-01

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Minimising the risk: reducing breast tissue dose in an adolescent female

International Nuclear Information System (INIS)

Thompson, Ann; Toe, Aimee; Ungureanu, Elena; Wolf, M.; Wirth, Andrew

2005-01-01

Breast cancer is amongst the leading radiation-associated, second malignancies that develop in patients after treatment for Hodgkin's disease. This risk is affected by two main factors: 1. The age of the patient at the time of radiotherapy; and 2. The dose received by the breast tissue The adolescent female thus faces an exceptionally high risk, as breast tissue at this age is undergoing rapid developmental growth and small doses of radiation exposure could be carcinogenic. This case report of a fifteen-year-old girl who received radiotherapy for Hodgkin's disease demonstrates how radiation therapists worked together with the radiation oncologists and medical physicists to provide an optimal treatment plan for a high-risk patient. Copyright (2005) Australian Institute of Radiography

Discriminant analysis of normal and malignant breast tissue based upon INAA investigation of elemental concentration

International Nuclear Information System (INIS)

Kwanhoong Ng; Senghuat Ong; Bradley, D.A.; Laimeng Looi

1997-01-01

Discriminant analysis of six trace element concentrations measured by instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant and histologically normal human breast tissues shows the technique to be a potentially valuable clinical tool for making malignant-normal classification. Nonparametric discriminant analysis is performed for the data obtained. Linear and quadratic discriminant analyses are also carried out for comparison. For this data set a formal analysis shows that the elements which may be useful in distinguishing between malignant and normal tissues are Ca, Rb and Br, providing correct classification for 24 out of 26 normal samples and 22 out of 26 malignant samples. (Author)

Influence of nuclear interactions in body tissues on tumor dose in carbon-ion radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Inaniwa, T., E-mail: taku@nirs.go.jp; Kanematsu, N. [Medical Physics Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555 (Japan); Tsuji, H.; Kamada, T. [Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2015-12-15

Purpose: In carbon-ion radiotherapy treatment planning, the planar integrated dose (PID) measured in water is applied to the patient dose calculation with density scaling using the stopping power ratio. Since body tissues are chemically different from water, this dose calculation can be subject to errors, particularly due to differences in inelastic nuclear interactions. In recent studies, the authors proposed and validated a PID correction method for these errors. In the present study, the authors used this correction method to assess the influence of these nuclear interactions in body tissues on tumor dose in various clinical cases. Methods: Using 10–20 cases each of prostate, head and neck (HN), bone and soft tissue (BS), lung, liver, pancreas, and uterine neoplasms, the authors first used treatment plans for carbon-ion radiotherapy without nuclear interaction correction to derive uncorrected dose distributions. The authors then compared these distributions with recalculated distributions using the nuclear interaction correction (corrected dose distributions). Results: Median (25%/75% quartiles) differences between the target mean uncorrected doses and corrected doses were 0.2% (0.1%/0.2%), 0.0% (0.0%/0.0%), −0.3% (−0.4%/−0.2%), −0.1% (−0.2%/−0.1%), −0.1% (−0.2%/0.0%), −0.4% (−0.5%/−0.1%), and −0.3% (−0.4%/0.0%) for the prostate, HN, BS, lung, liver, pancreas, and uterine cases, respectively. The largest difference of −1.6% in target mean and −2.5% at maximum were observed in a uterine case. Conclusions: For most clinical cases, dose calculation errors due to the water nonequivalence of the tissues in nuclear interactions would be marginal compared to intrinsic uncertainties in treatment planning, patient setup, beam delivery, and clinical response. In some extreme cases, however, these errors can be substantial. Accordingly, this correction method should be routinely applied to treatment planning in clinical practice.

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

Science.gov (United States)

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Research on the dose of the tissues located outside the treatment field when breast cancer was irradiated by linear accelerator

International Nuclear Information System (INIS)

Tu Yu; Zhou Juying; Jiang Dezhi; Qin Songbing

1999-10-01

The purpose of study was to determine the dose of the tissues which located outside the treatment field, when breast cancer was irradiated by 9 MeV electron-beam and 6 MV-X ray after operation. A search for decreasing the dose of the tissues outside the treatment field was made. Clinically relevant treatment fields were simulated on a tissue-equivalent material phantom and subsequently irradiated with 9 MeV electron-beam and 6 MV-X ray. TLD were used to measure absorbed doses. The prescribed dose of breast cancer region was 50.0 Gy, region-lymph-nodes were 60.0 Gy, each exposure dose was 2.0 Gy. In breast cancer region, if only with 9 MeV electron-beam, the dose of the tissues located outside the treatment field were from 29.0 cGy to 295.5 cGy, when shielded with Pb lump, the doses of the tissues outside the treatment field may descended 9.4%-53.6%; if only with 6 MV-X ray, the doses of aforementioned tissues were from 32.0 cGy to 206.7 cGy, when shielded with Pb lump, the doses of the tissues outside the treatment field descended 19.7%-56.6%. In region-lymph-nodes, with 6 MV-X ray, the doses of aforementioned tissues were from 22.5 cGy to 1650.9 cGy, when shielded with Pb lump, the doses of the tissues outside the treatment field descended 19.7-65.6%. If mix-irradiation (9 MeV electron-beam vs. 6 MV-X ray 2:3) was used, the doses outside field would be lower than only used 9 MeV electron-beam or 6 MV-X ray were used

Analysis of ethyl acrylate (EA) and acrylic acid (AA) residues from rat tissues following oral ea dosing

International Nuclear Information System (INIS)

Udinsky, J.R.; Frederick, C.B.

1990-01-01

Gavage dosing of rats with EA at high dose levels (100 or 200 mg/kg) has resulted in tumors at the dosing site, forestomach (FST), but no lesions of the glandular stomach (GST) or other remote tissues. Since previous in vitro studies have demonstrated that EA is very rapidly metabolized to AA and glutathione conjugates, EA and AA residues were analyzed 0-24 hr following gavage dosing of non-fasted F-344/N male rats with [1- 14 C]EA in corn oil at 10, 50, and 200 mg/kg. Analysis of total 14 C indicated that the dose solution was primarily in the FST at ≥5 min after dosing, although 14 C was detected in the GST, duodenum, and small intestine (attributed to distension of the FST and leakage from the FST to the GST). HPLC analysis of the gut contents, gut wall, liver, kidneys, lungs, and blood indicated that EA and AA could only be detected at ≥15 min in the FST and GST contents, and in the FST tissue. AA alone was detected in the GST tissue, duodenum tissue and contents, and small intestine tissue and contents. The minimum level of detection was 0.0005% of the dose. The remaining 14 C was primarily attributed to binding to the gut contents or bioincorporation of AA. The detection of EA and AA residues only in the upper gastrointestinal tract following gavage dosing is consistent with rapid detoxification of EA by hydrolysis and conjugation which prevents toxicity at sites remote form the site of dosing

Comparison of image quality and visibility of normal and abnormal findings at submillisievert chest CT using filtered back projection, iterative model reconstruction (IMR) and iDose{sup 4}™

Energy Technology Data Exchange (ETDEWEB)

Laqmani, Azien, E-mail: a.laqmani@uke.de [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Avanesov, Maxim; Butscheidt, Sebastian; Kurfürst, Maximilian [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Sehner, Susanne [Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Schmidt-Holtz, Jakob; Derlin, Thorsten; Behzadi, Cyrus [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Nagel, Hans D. [Science & Technology for Radiology, Fritz-Reuter-Weg 5f, 21244 Buchholz, Germany, (Germany); Adam, Gerhard; Regier, Marc [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

2016-11-15

Objective: To compare both image quality and visibility of normal and abnormal findings at submillisievert chest CT (smSv-CT) using filtered back projection (FBP) and the two different iterative reconstruction (IR) techniques iterative model reconstruction (IMR) and iDose{sup 4}™. Materials and methods: This institutional review board approved study was based on retrospective interpretation of clinically indicated acquired data. The requirement to obtain informed consent was waived. 81 patients with suspected pneumonia underwent smSv-CT (Brilliance iCT, Philips Healthcare; mean effective dose: 0.86 ± 0.2 mSv). Data were reconstructed using FBP and two different IR techniques iDose{sup 4}™ and IMR (Philips Healthcare) at various iteration levels. Objective image noise (OIN) was measured. Two experienced readers independently assessed all images for image noise, image appearance and visibility of normal anatomic and abnormal findings. A random intercept model was used for statistical analysis. Results: Compared to FBP and iDose{sup 4}™, IMR reduced OIN up to 88% and 72%, respectively (p < 0.001). A mild blotchy image appearance was seen in IMR images, affecting diagnostic confidence. iDose{sup 4}™ images provided satisfactory to good image quality for visibility of normal and abnormal findings and were superior to FBP (p < 0.001). IMR images were significantly inferior for visibility of normal structures compared to iDose{sup 4}™, while being superior for visibility of abnormal findings except for reticular pattern (p < 0.001). Conclusion: IMR results for visibility of normal and abnormal lung findings are heterogeneous, indicating that IMR may not represent a priority technique for clinical routine. iDose{sup 4}™ represents a suitable method for evaluation of lung tissue at submillisievert chest CT.

Sensitivity of low energy brachytherapy Monte Carlo dose calculations to uncertainties in human tissue composition

Energy Technology Data Exchange (ETDEWEB)

Landry, Guillaume; Reniers, Brigitte; Murrer, Lars; Lutgens, Ludy; Bloemen-Van Gurp, Esther; Pignol, Jean-Philippe; Keller, Brian; Beaulieu, Luc; Verhaegen, Frank [Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN (Netherlands); Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Departement de Radio-Oncologie et Centre de Recherche en Cancerologie, de l' Universite Laval, CHUQ, Pavillon L' Hotel-Dieu de Quebec, Quebec G1R 2J6 (Canada) and Departement de Physique, de Genie Physique et d' Optique, Universite Laval, Quebec G1K 7P4 (Canada); Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN (Netherlands) and Medical Physics Unit, McGill University, Montreal General Hospital, Montreal, Quebec H3G 1A4 (Canada)

2010-10-15

Purpose: The objective of this work is to assess the sensitivity of Monte Carlo (MC) dose calculations to uncertainties in human tissue composition for a range of low photon energy brachytherapy sources: {sup 125}I, {sup 103}Pd, {sup 131}Cs, and an electronic brachytherapy source (EBS). The low energy photons emitted by these sources make the dosimetry sensitive to variations in tissue atomic number due to the dominance of the photoelectric effect. This work reports dose to a small mass of water in medium D{sub w,m} as opposed to dose to a small mass of medium in medium D{sub m,m}. Methods: Mean adipose, mammary gland, and breast tissues (as uniform mixture of the aforementioned tissues) are investigated as well as compositions corresponding to one standard deviation from the mean. Prostate mean compositions from three different literature sources are also investigated. Three sets of MC simulations are performed with the GEANT4 code: (1) Dose calculations for idealized TG-43-like spherical geometries using point sources. Radial dose profiles obtained in different media are compared to assess the influence of compositional uncertainties. (2) Dose calculations for four clinical prostate LDR brachytherapy permanent seed implants using {sup 125}I seeds (Model 2301, Best Medical, Springfield, VA). The effect of varying the prostate composition in the planning target volume (PTV) is investigated by comparing PTV D{sub 90} values. (3) Dose calculations for four clinical breast LDR brachytherapy permanent seed implants using {sup 103}Pd seeds (Model 2335, Best Medical). The effects of varying the adipose/gland ratio in the PTV and of varying the elemental composition of adipose and gland within one standard deviation of the assumed mean composition are investigated by comparing PTV D{sub 90} values. For (2) and (3), the influence of using the mass density from CT scans instead of unit mass density is also assessed. Results: Results from simulation (1) show that variations

Interspecies comparison of the tissue distribution of WR-2721, a radioprotective drug

International Nuclear Information System (INIS)

Washburn, L.C.; Rafter, J.J.; Hayes, R.L.; Yuhas, J.M.

1975-01-01

Pre-irradiation intravenous administration of the radioprotective drug S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR-2721) has potential value in radiotherapy because it doubles the radiation resistance of normal mouse tissues while affording only minimal protection to tumors. Deficient deposition of WR- 2721 in tumor tissue has recently been demonstrated and this is thought to be a major reason for the preferential protection of normal tissues by the drug. Data originally obtained in studies using the mouse and rat indicated that the tissue distribution of WR-2721 was possibly more closely related to dose per unit surface area than to dose per unit weight. To test this hypothesis an interspecies comparison of the tissue distribution of 35 S-labeled WR-2721 was carried out in normal mice, rats, rabbits, and dogs at 15 and 30 minutes after intravenous administration. Results suggest that the surface area and body weight exert equal effects on the tissue concentration of WR-2721. The results further suggest that lower absolute doses of WR-2721 in the human, possibly as low as 20 mg/kg, may provide a radioprotective effect equivalent to that produced from 100 mg/kg in the mouse, i.e., a 50 to 80 percent increase in radiation resistance (CH)

Accurate tissue area measurements with considerably reduced radiation dose achieved by patient-specific CT scan parameters

DEFF Research Database (Denmark)

Brandberg, J.; Bergelin, E.; Sjostrom, L.

2008-01-01

A low-dose technique was compared with a standard diagnostic technique for measuring areas of adipose and muscle tissue and CT numbers for muscles in a body composition application. The low-dose technique was intended to keep the expected deviation in the measured area of adipose and muscle tissu...

Non-uniform dwell times in line source high dose rate brachytherapy: physical and radiobiological considerations

International Nuclear Information System (INIS)

Jones, B.; Tan, L.T.; Freestone, G.; Bleasdale, C.; Myint, S.; Littler, J.

1994-01-01

The ability to vary source dwell times in high dose rate (HDR) brachytherapy allows for the use of non-uniform dwell times along a line source. This may have advantages in the radical treatment of tumours depending on individual tumour geometry. This study investigates the potential improvements in local tumour control relative to adjacent normal tissue isoeffects when intratumour source dwell times are increased along the central portion of a line source (technique A) in radiotherapy schedules which include a relatively small component of HDR brachytherapy. Such a technique is predicted to increase the local control for tumours of diameters ranging between 2 cm and 4 cm by up to 11% compared with a technique in which there are uniform dwell times along the line source (technique B). There is no difference in the local control rates for the two techniques when used to treat smaller tumours. Normal tissue doses are also modified by the technique used. Technique A produces higher normal tissue doses at points perpendicular to the centre of the line source and lower dose at points nearer the ends of the line source if the prescription point is not in the central plane of the line source. Alternatively, if the dose is prescribed at a point in the central plane of the line source, the dose at all the normal tissue points are lower when technique A is used. (author)

A trial of radiation dose prescription based on dose-cell survival formula

International Nuclear Information System (INIS)

Allen, E.P.

1984-01-01

Radiation treatment has been prescribed for 379 basal cell carcinomata on the basis of a selected equivalent single dose derived from the standard multi-target dose-cell survival formula using values of m = 2 and Do = 130 rads for orthovoltage x-rays. The results suggest that the approach provides a flexible and acceptable alternative to prescription by total dose or by Nominal Standard Dose. It is submitted that Total Dose is an inadequate expression of radiobiological effects: that the NSD and related systems are valuable measures of the ability of normal tissues to recover from radiation damage: and that a parallel measure of the degree of tumour depopulation has become necessary to allow further progress in alternative fractionation schedules

Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

International Nuclear Information System (INIS)

Maase, H. van der

1986-01-01

The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

International Nuclear Information System (INIS)

Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

2009-01-01

Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

Trace element determinations in brain tissues from normal and clinically demented individuals

International Nuclear Information System (INIS)

Saiki, Mitiko; Genezini, Frederico A.; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson

2013-01-01

Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

Energy Technology Data Exchange (ETDEWEB)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Science.gov (United States)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-03-01

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

International Nuclear Information System (INIS)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-01-01

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Energy Technology Data Exchange (ETDEWEB)

Samani, Abbas [Department of Medical Biophysics/Electrical and Computer Engineering, University of Western Ontario, Medical Sciences Building, London, Ontario, N6A 5C1 (Canada); Zubovits, Judit [Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada); Plewes, Donald [Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada)

2007-03-21

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

Investigation of real tissue water equivalent path lengths using an efficient dose extinction method

Science.gov (United States)

Zhang, Rongxiao; Baer, Esther; Jee, Kyung-Wook; Sharp, Gregory C.; Flanz, Jay; Lu, Hsiao-Ming

2017-07-01

For proton therapy, an accurate conversion of CT HU to relative stopping power (RSP) is essential. Validation of the conversion based on real tissue samples is more direct than the current practice solely based on tissue substitutes and can potentially address variations over the population. Based on a novel dose extinction method, we measured water equivalent path lengths (WEPL) on animal tissue samples to evaluate the accuracy of CT HU to RSP conversion and potential variations over a population. A broad proton beam delivered a spread out Bragg peak to the samples sandwiched between a water tank and a 2D ion-chamber detector. WEPLs of the samples were determined from the transmission dose profiles measured as a function of the water level in the tank. Tissue substitute inserts and Lucite blocks with known WEPLs were used to validate the accuracy. A large number of real tissue samples were measured. Variations of WEPL over different batches of tissue samples were also investigated. The measured WEPLs were compared with those computed from CT scans with the Stoichiometric calibration method. WEPLs were determined within  ±0.5% percentage deviation (% std/mean) and  ±0.5% error for most of the tissue surrogate inserts and the calibration blocks. For biological tissue samples, percentage deviations were within  ±0.3%. No considerable difference (extinction measurement took around 5 min to produce ~1000 WEPL values to be compared with calculations. This dose extinction system measures WEPL efficiently and accurately, which allows the validation of CT HU to RSP conversions based on the WEPL measured for a large number of samples and real tissues.

Results of dose calculations for NET accidental and normal operation releases of tritium and activation products

International Nuclear Information System (INIS)

Raskob, W.; Hasemann, I.

1992-08-01

This report documents conditions, data and results of dose calculations for accidental and normal operation releases of tritium and activation products, performed within the NET subtask SEP2.2 ('NET-Benchmark') of the European Fusion Technology Programme. For accidental releases, the computer codes UFOTRI and COSYMA for assessing the radiological consequences, have been applied for both deterministic and probabilistic calculations. The influence on dose estimates of different release times (2 minutes / 1 hour), two release heights (10 m / 150 m), two chemical forms of tritium (HT/HTO), and two different model approaches for the deposition velocity of HTO on soil was investigated. The dose calculations for normal operation effluents were performed using the tritium model of the German regulatory guidelines, parts of the advanced dose assessment model NORMTRI still under development, and the statistical atmospheric dispersion model ISOLA. Accidental and normal operation source terms were defined as follows: 10g (3.7 10 15 Bq) for accidental tritium releases, 10 Ci/day (3.7 10 11 Bq/day) for tritium releases during normal operation and unit releases of 10 9 Bq for accidental releases of activation products and fission products. (orig./HP) [de

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

The impact of dose calculation algorithms on partial and whole breast radiation treatment plans

International Nuclear Information System (INIS)

Basran, Parminder S; Zavgorodni, Sergei; Berrang, Tanya; Olivotto, Ivo A; Beckham, Wayne

2010-01-01

This paper compares the calculated dose to target and normal tissues when using pencil beam (PBC), superposition/convolution (AAA) and Monte Carlo (MC) algorithms for whole breast (WBI) and accelerated partial breast irradiation (APBI) treatment plans. Plans for 10 patients who met all dosimetry constraints on a prospective APBI protocol when using PBC calculations were recomputed with AAA and MC, keeping the monitor units and beam angles fixed. Similar calculations were performed for WBI plans on the same patients. Doses to target and normal tissue volumes were tested for significance using the paired Student's t-test. For WBI plans the average dose to target volumes when using PBC calculations was not significantly different than AAA calculations, the average PBC dose to the ipsilateral breast was 10.5% higher than the AAA calculations and the average MC dose to the ipsilateral breast was 11.8% lower than the PBC calculations. For ABPI plans there were no differences in dose to the planning target volume, ipsilateral breast, heart, ipsilateral lung, or contra-lateral lung. Although not significant, the maximum PBC dose to the contra-lateral breast was 1.9% higher than AAA and the PBC dose to the clinical target volume was 2.1% higher than AAA. When WBI technique is switched to APBI, there was significant reduction in dose to the ipsilateral breast when using PBC, a significant reduction in dose to the ipsilateral lung when using AAA, and a significant reduction in dose to the ipsilateral breast and lung and contra-lateral lung when using MC. There is very good agreement between PBC, AAA and MC for all target and most normal tissues when treating with APBI and WBI and most of the differences in doses to target and normal tissues are not clinically significant. However, a commonly used dosimetry constraint, as recommended by the ASTRO consensus document for APBI, that no point in the contra-lateral breast volume should receive >3% of the prescribed dose needs

Dose determination algorithms for a nearly tissue equivalent multi-element thermoluminescent dosimeter

International Nuclear Information System (INIS)

Moscovitch, M.; Chamberlain, J.; Velbeck, K.J.

1988-01-01

In a continuing effort to develop dosimetric systems that will enable reliable interpretation of dosimeter readings in terms of the absorbed dose or dose-equivalent, a new multi-element TL dosimeter assembly for Beta and Gamma dose monitoring has been designed. The radiation-sensitive volumes are four LiF-TLD elements, each covered by its own unique filter. For media-matching, care has been taken to employ nearly tissue equivalent filters of thicknesses of 1000 mg/cm 2 and 300 mg/cm 2 for deep dose and dose to the lens-of-the-eye measurements respectively. Only one metal filter (Cu) is employed to provide low energy photon discrimination. A Thin TL element (0.09 mm thick) is located behind an open window designed to improve the energy under-response to low energy beta rays and to provide closer estimate of the shallow dose equivalent. The deep and shallow dose equivalents are derived from the correlation of the response of the various TL elements to the above quantities through computations based on previously defined relationships obtained from experimental results. The theoretical formalization for the dose calculation algorithms is described in detail, and provides a useful methodology which can be applied to different tissue-equivalent dosimeter assemblies. Experimental data has been obtained by performing irradiation according to the specifications established by DOELAP, using 27 types of pure and mixed radiation fields including Cs-137 gamma rays, low energy photons down to 20 keV, Sr/Y-90, Uranium, and Tl-204 beta particles

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

Science.gov (United States)

Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-05-21

The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

International Nuclear Information System (INIS)

Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-01-01

The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

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Knüchel Ruth

2008-05-01

Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

Science.gov (United States)

Jaramillo-Rodríguez, Yolanda; Cerda-Flores, Ricardo M; Ruiz-Ramos, Ruben; López-Márquez, Francisco C; Calderón-Garcidueñas, Ana Laura

2014-04-01

Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

Normal tissue tolerance to external beam radiation therapy: Adult bone

International Nuclear Information System (INIS)

Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

2010-01-01

Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

International Nuclear Information System (INIS)

Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S

2016-01-01

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V_2_0 and V_5 to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm"3. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V_2_0 (+3.1%) and V_5 (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

Energy Technology Data Exchange (ETDEWEB)

Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S [Montefiore Medical Center, Bronx, NY (United States)

2016-06-15

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates

Improved tissue assignment using dual-energy computed tomography in low-dose rate prostate brachytherapy for Monte Carlo dose calculation

Energy Technology Data Exchange (ETDEWEB)

Côté, Nicolas [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4 (Canada); Bedwani, Stéphane [Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada); Carrier, Jean-François, E-mail: jean-francois.carrier.chum@ssss.gouv.qc.ca [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4, Canada and Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada)

2016-05-15

Purpose: An improvement in tissue assignment for low-dose rate brachytherapy (LDRB) patients using more accurate Monte Carlo (MC) dose calculation was accomplished with a metallic artifact reduction (MAR) method specific to dual-energy computed tomography (DECT). Methods: The proposed MAR algorithm followed a four-step procedure. The first step involved applying a weighted blend of both DECT scans (I {sub H/L}) to generate a new image (I {sub Mix}). This action minimized Hounsfield unit (HU) variations surrounding the brachytherapy seeds. In the second step, the mean HU of the prostate in I {sub Mix} was calculated and shifted toward the mean HU of the two original DECT images (I {sub H/L}). The third step involved smoothing the newly shifted I {sub Mix} and the two original I {sub H/L}, followed by a subtraction of both, generating an image that represented the metallic artifact (I {sub A,(H/L)}) of reduced noise levels. The final step consisted of subtracting the original I {sub H/L} from the newly generated I {sub A,(H/L)} and obtaining a final image corrected for metallic artifacts. Following the completion of the algorithm, a DECT stoichiometric method was used to extract the relative electronic density (ρ{sub e}) and effective atomic number (Z {sub eff}) at each voxel of the corrected scans. Tissue assignment could then be determined with these two newly acquired physical parameters. Each voxel was assigned the tissue bearing the closest resemblance in terms of ρ{sub e} and Z {sub eff}, comparing with values from the ICRU 42 database. A MC study was then performed to compare the dosimetric impacts of alternative MAR algorithms. Results: An improvement in tissue assignment was observed with the DECT MAR algorithm, compared to the single-energy computed tomography (SECT) approach. In a phantom study, tissue misassignment was found to reach 0.05% of voxels using the DECT approach, compared with 0.40% using the SECT method. Comparison of the DECT and SECT D

Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

Science.gov (United States)

Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

2014-01-01

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

MOSFET dosimeter depth-dose measurements in heterogeneous tissue-equivalent phantoms at diagnostic x-ray energies

International Nuclear Information System (INIS)

Jones, A.K.; Pazik, F.D.; Hintenlang, D.E.; Bolch, W.E.

2005-01-01

The objective of the present study was to explore the use of the TN-1002RD metal-oxide-semiconductor field effect transistor (MOSFET) dosimeter for measuring tissue depth dose at diagnostic photon energies in both homogeneous and heterogeneous tissue-equivalent materials. Three cylindrical phantoms were constructed and utilized as a prelude to more complex measurements within tomographic physical phantoms of pediatric patients. Each cylindrical phantom was constructed as a stack of seven 5-cm-diameter and 1-cm-thick discs of materials radiographically representative of either soft tissue (S), bone (B), or lung tissue (L) at diagnostic photon energies. In addition to a homogeneous phantom of soft tissue (SSSSSSS), two heterogeneous phantoms were constructed: SSBBSSS and SBLLBSS. MOSFET dosimeters were then positioned at the interface of each disc, and the phantoms were then irradiated at 66 kVp and 200 mAs. Measured values of absorbed dose at depth were then compared to predicated values of point tissue dose as determined via Monte Carlo radiation transport modeling. At depths exceeding 2 cm, experimental results matched the computed values of dose with high accuracy regardless of the dosimeter orientation (epoxy bubble facing toward or away from the x-ray beam). Discrepancies were noted, however, between measured and calculated point doses near the surface of the phantom (surface to 2 cm depth) when the dosimeters were oriented with the epoxy bubble facing the x-ray beam. These discrepancies were largely eliminated when the dosimeters were placed with the flat side facing the x-ray beam. It is therefore recommended that the MOSFET dosimeters be oriented with their flat sides facing the beam when they are used at shallow depths or on the surface of either phantoms or patients

Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

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Emara Marwan

2010-09-01

Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

Cancer and low dose responses in vivo: implications for radiation protection

International Nuclear Information System (INIS)

Mitchel, R.E.J.

2006-01-01

Full text: Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be genetically cancer prone. Mice heterozygous for the Tp 53 gene are cancer prone, and their increased risk from high doses was not different from Tp 53 normal mice. However, in either Tp 53 normal or heterozygous mice, a single low dose of low LET radiation given at low dose rate protected against both spontaneous and radiation-induced cancer by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp 53 function) overall risk is reduced below that of unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish radiation weighting factors (Wr) used in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate

The usefulness of metal markers for CTV-based dose prescription in high-dose-rate interstitial brachytherapy

International Nuclear Information System (INIS)

Yoshida, Ken; Mitomo, Masanori; Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Yoshida, Mineo

2002-01-01

We employ a clinical target volume (CTV)-based dose prescription for high-dose-rate (HDR) interstitial brachytherapy. However, it is not easy to define CTV and organs at risk (OAR) from X-ray film or CT scanning. To solve this problem, we have utilized metal markers since October 1999. Moreover, metal markers can help modify dose prescription. By regulating the doses to the metal markers, refining the dose prescription can easily be achieved. In this research, we investigated the usefulness of the metal markers. Between October 1999 and May 2001, 51 patients were implanted with metal markers at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Osaka National Hospital (ONH) and Sanda City Hospital (SCH). Forty-nine patients (head and neck: 32; pelvis: 11; soft tissue: 3; breast: 3) using metal markers were analyzed. During operation, we implanted 179 metal markers (49 patients) to CTV and 151 markers (26 patients) to OAR. At treatment planning, CTV was reconstructed judging from the metal markers, applicator position and operation records. Generally, we prescribed the tumoricidal dose to an isodose surface that covers CTV. We also planned to limit the doses to OAR lower than certain levels. The maximum normal tissue doses were decided 80%, 150%, 100%, 50% and 200% of the prescribed doses for the rectum, the urethra, the mandible, the skin and the large vessel, respectively. The doses to the metal markers using CTV-based dose prescription were generated. These were compared with the doses theoretically calculated with the Paris system. Treatment results were also investigated. The doses to the 158 metal markers (42 patients) for CTV were higher than ''tumoricidal dose''. In 7 patients, as a result of compromised dose prescription, 9 markers were lower than the tumoricidal dose. The other 12 markers (7%) were excluded from dose evaluation because they were judged as miss-implanted. The doses to the 142 metal markers (24 patients) for OAR were lower

Dose optimization of intra-operative high dose rate interstitial brachytherapy implants for soft tissue sarcoma

Directory of Open Access Journals (Sweden)

Jamema Swamidas

2009-01-01

Full Text Available Objective : A three dimensional (3D image-based dosimetric study to quantitatively compare geometric vs. dose-point optimization in combination with graphical optimization for interstitial brachytherapy of soft tissue sarcoma (STS. Materials and Methods : Fifteen consecutive STS patients, treated with intra-operative, interstitial Brachytherapy, were enrolled in this dosimetric study. Treatment plans were generated using dose points situated at the "central plane between the catheters", "between the catheters throughout the implanted volume", at "distances perpendicular to the implant axis" and "on the surface of the target volume" Geometrically optimized plans had dose points defined between the catheters, while dose-point optimized plans had dose points defined at a plane perpendicular to the implant axis and on the target surface. Each plan was graphically optimized and compared using dose volume indices. Results : Target coverage was suboptimal with coverage index (CI = 0.67 when dose points were defined at the central plane while it was superior when the dose points were defined at the target surface (CI=0.93. The coverage of graphically optimized plans (GrO was similar to non-GrO with dose points defined on surface or perpendicular to the implant axis. A similar pattern was noticed with conformity index (0.61 vs. 0.82. GrO were more conformal and less homogeneous compared to non-GrO. Sum index was superior for dose points defined on the surface of the target and relatively inferior for plans with dose points at other locations (1.35 vs. 1.27. Conclusions : Optimization with dose points defined away from the implant plane and on target results in superior target coverage with optimal values of other indices. GrO offer better target coverage for implants with non-uniform geometry and target volume.

Establishing the impact of temporary tissue expanders on electron and photon beam dose distributions.

Science.gov (United States)

Asena, A; Kairn, T; Crowe, S B; Trapp, J V

2015-05-01

This study investigates the effects of temporary tissue expanders (TTEs) on the dose distributions in breast cancer radiotherapy treatments under a variety of conditions. Using EBT2 radiochromic film, both electron and photon beam dose distribution measurements were made for different phantoms, and beam geometries. This was done to establish a more comprehensive understanding of the implant's perturbation effects under a wider variety of conditions. The magnetic disk present in a tissue expander causes a dose reduction of approximately 20% in a photon tangent treatment and 56% in electron boost fields immediately downstream of the implant. The effects of the silicon elastomer are also much more apparent in an electron beam than a photon beam. Evidently, each component of the TTE attenuates the radiation beam to different degrees. This study has demonstrated that the accuracy of photon and electron treatments of post-mastectomy patients is influenced by the presence of a tissue expander for various beam orientations. The impact of TTEs on dose distributions establishes the importance of an accurately modelled high-density implant in the treatment planning system for post-mastectomy patients. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.